Jump to content

  • Log in with Facebook Log in with Twitter Log in with Windows Live Log In with Google      Sign In   
  • Create Account

Submit your paper to J Biol Methods today!

whcaroline's Content

There have been 66 items by whcaroline (Search limited from 20-July 18)

Sort by                Order  

#179210 MMP inhibitors may treat TB

Posted by whcaroline on 25 May 2017 - 10:31 AM in Immunology Products

A paper (Matrix Degradation in Human Immunodeficiency Virus Type 1–Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study) in Clinical Infectious Diseases has revealed that MMP inhibitors might help treat TB.
Tuberculosis (TB) and human immunodeficiency virus (HIV) are both global epidemics that claim many people's lives each year. The bacterium Mycobacterium tuberculosis (Mtb) is the cause agent of TB. According to the Centers for Disease Control and Prevention (CDC), in 2015, TB affected 10.4 million people and was responsible for 1.8 million deaths worldwide.
Prognosis of TB has greatly improved over the past several decades. If the correct drugs are taken for the right amount of time, more than 90% of all TB cases can be cured. TB treatment usually includes multiple antibiotics, such as isoniazid, rifampin, ethambutol, and pyrazinamide.
However, TB in people with HIV is much more difficult to treat. People living with HIV are 24-28 times more likely to develop TB than people without HIV, says the WHO. This is because HIV infection weakens the immune system. TB is the leading cause of death among HIV-infected people. Antibiotics for TB may interact with antiretroviral therapy (ART) drugs used to treat HIV, leading to a condition called tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS). TB-IRIS is characterized by an excessive immune response against the Mtb bacteria, which causes further lung damage. But the underlying mechanism is not well-defined.
Previous studies have shown that matrix metalloproteinases (MMPs), a family of enzymes responsible for degrading the main structural protein called collagen, may drive tissue destruction in TB. In this study, lead researcher Naomi Walker and colleagues measured MMP concentrations in sputum and plasma in HIV–infected and –uninfected TB patients and controls.
They found that MMP activity differed between HIV–infected and –uninfected TB patients and was related to specific TB clinical phenotypes. Patients with HIV/TB co-infection had lower lung MMP concentrations and milder lung damage than TB patients without HIV. Additionally, TB patients who were most infectious with worse lung damage had the highest MMP levels. Collectively, the results indicate that MMP activity is associated with lung damage.
Further experiments in vitro showed that the MMP inhibitor doxycycline could suppress matrix destruction induced by TB, suggesting that MMP inhibition is a potential host-directed therapy strategy for TB. Doxycycline is an antibiotic that is already used to treat infections caused by bacteria and protozoa. This study highlights the potential use of doxycycline in the prevention and treatment of TB.
In conclusion, the study has identified differences in immune responses between TB patients with and without HIV and would lead to new treatment options for TB. The study is a collaboration of the University of Cape Town, the Imperial College London, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Francis Crick Institute, and the University of Southampton.  (Cusabio provides MMP and related bioproducts. http://www.cusabio.com/)

#179208 PD-L1 may inhibit pain in certain types of cancer

Posted by whcaroline on 24 May 2017 - 09:33 AM in Immunology Products

New research provides a way to predict the effectiveness of immunotherapy. The research, carried out by Duke University Medical Center, Nantong University, Gachon University, and Fudan University, shows that D-L1 (programmed death-ligand 1) acts not only on immune cells but also on neurons that signal pain.
Immunotherapy has emerged as an important treatment for cancer patients. It uses substances that restore or enhance the immune system's natural ability to fight cancer. However, clinicians note a variety of side effects such as skin rashes, allergic reactions, endocrine disorders, and heart damage that may accompany immunotherapy. Data show that immunotherapy agents work for only around a fifth of patients.
PD-L1 is a ligand of PD-1 (programmed cell death protein 1), a cell surface receptor that plays a key role in down-regulating the immune system. PD-L1 and PD-1 belong to the family of immune checkpoint proteins, which can limit the development of the T cell response. Blocking the PD-L1/PD-1 pathway represents a strategy for immunotherapy. For example, a common cancer drug -- nivolumab-- works as checkpoint inhibitor that blocks the PD-L1/PD-1 interaction.
Cancer cells can escape the body defense mechanisms in different ways. Multiple cancer types, such as melanoma, manage to inhibit the immune system by generating PD-L1. The feeling of pain is another defense mechanism that tells a person to protect the injured or diseased area. Generally, when cancer progresses to an aggressive form, cancer cells will produce a large number of pain-inducing chemicals that stimulate pain-sensing neurons. In cancer patients, the pain can be unbearable.
While studying pain, the team surprisingly found that mice with melanoma did not exhibit signs of pain seen in mice with other types of cancer. The researchers asked if there was a link between the expression of PD-L1 by melanoma cells and pain insensitivity observed in these animals. To address this question, they treated mice with nivolumab and used a test to evaluate their pain sensitivity. Results showed that treatment with nivolumab made mice more sensitive to pain as well as triggered spontaneous pain in mice with melanoma. In contrast, injection of PD-L1 reduced pain sensitivity in mouse models of inflammatory, neuropathic or bone cancer pain.
The team then further explored this function of PD-L1 by examining sensory neurons at the dorsal root ganglion and discovered that PD-L1 potently suppressed nociceptive neuron excitability. Together, these data suggest that the checkpoint protein PD-L1 may act as a pain inhibitor and a neuromodulator. The discovery may aid in the development of new painkillers as well as new ways to predict the effectiveness of immunotherapy agents that target the PD-L1/PD-1 pathway.
The study, “PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1,”is published in Nature Neuroscience. Gang Chen is the first author. (Cusabio provides PD-L1, and PD-1 proteins/antibodies. http://www.cusabio.com/)

#179207 Potent antibodies protect against ebolaviruses

Posted by whcaroline on 20 May 2017 - 03:44 AM in Immunology Products

Since 2014, the lethal Ebola virus has swept many countries on the planet, particularly Liberia, Sierra Leone, and Guinea in West Africa. Ebola becomes an emerging infectious disease for which there is no known cure. Now, making progress toward a vaccine and therapy against Ebola, researchers reporting in Cell have identified natural human antibodies with the potential to provide broad protection against Ebolaviruses.
Therapies based on monoclonal antibody has shown promise for treatment of Ebola infections. However, one thing that limits their application is that most antibody therapies target just one specific ebolavirus due to their species-specific recognition of the viral glycoprotein (GP). One experimental therapy called ZMappTM, which comprises thress chimeric monclonal antibodies, is specific for Ebola virus, or called Zaire ebolavirus, but is ineffective against two other ebolaviruses known as Sudan virus and Bundibugyo virus.
The genus Ebolavirus is included in the family Filoviridae, order Mononegavirales. In addition to Zaire ebolavirus, Sudan virus and Bundibugyo virus, there are two other virus species that belong to this genus: Ta  Forest ebolavirus and Reston ebolavirus. Essentially, it is very difficult to predict which species will cause the next epidemic. So developing a broadly effective therapy that treats all ebolaviruses is a reasonable strategy in the fight against these lethal pathogens.
The new study, led by John Dye at U.S. Army Medical Research Institute of Infectious Diseases, Kartik Chandran at Albert Einstein College of Medicine, and Zachary Bornholdt at Mapp Biopharmaceutical, showed that two potent antibodies from a human survivor might be used as broadly effective immunotherapeutics and vaccines.
The team previously separated 349 different monoclonal antibodies from a survivor of the 2013-16 Ebola epidemic. For this work, by analyzing these antibodies, the team discovered two antibodies, ADI-15878 and ADI-15742, that effectively neutralized all the five ebolavirus species. Treatment with the antibodies protected animals that were exposed to Ebola virus, Bundibugyo virus and Sudan virus.
The researchers then looked at how the antibodies work at a molecular level. These antibodies recognize a critical and conserved element of the viral membrane fusion machinery, and inhibit viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes. Overall, these results could have implications in prevention and treatment of ebolaviruses. (CusAb strives to provide the excellent products such as GFAP Monoclonal Antibody for researchers.)

#179205 Researchers studying pancreatic cancer plan to test a new antibody

Posted by whcaroline on 18 May 2017 - 05:21 AM in Immunology Products

Cancer is a class of diseases characterized by out-of control cell growth. There are more than 100 different types of cancer. Among them, pancreatic cancer is among the most common and fatal. At the time of diagnosis, the vast majority of patients with pancreatic cancer have locally advanced or distant metastatic disease that can not by removed by surgery. Pancreatic cancer is considered Stage IV if it has spread to distant locations in the body. The five-year survival rate of pancreatic cancer is strongly correlated with disease stages; those with Stage IV exocrine pancreatic cancer has a five-year survival rate of about 1%. Effective treatments are in urgent need.
Now scientists from the University of Cincinnati (UC) have been scrambling for ways to fight against pancreatic cancer. Vladimir Bogdanov, PhD, a researcher and assistant professor in the UC College of Medicine Department of Internal Medicine’s Division of Hematology/Oncology, recently received a $300,000 grant from the Pancreatic Cancer Action Network. With the grant, Dr. Bogdanov and colleagues will be able to evaluate the efficacy of an experimental drug that targets alternatively spliced Tissue Factor (asTF) in treating pancreatic cancer.
asTF is a protein that functions to promote neovascularization and monocyte recruitment via integrin ligation. In a 2013 study, Dr. Bogdanov found that asTF is highly expressed in human PDAC (pancreatic ductal adenocarcinoma) tumor tissue but not in normal pancreas, and it promotes tumor metastasis in an orthotopic model of PDAC. Then Bogdanov’s team further explored the function of asTF in pancreatic cancer. Results showed that asTF expression and release into tissues is often elevated in pancreatic cancer and it binds cell surface molecules called beta1 integrins, which triggers processes that drive cancer progression. Further experiments in animals showed that inhibiting asTF suppressed pancreatic cancer growth.
Recently, the team developed a monoclonal antibody that targets asTF. The antibody, called RabMab1, will be tested in animal models of pancreatic cancer. Besides, the researchers will also study whether asTF levels in the blood of pancreas cancer patients could aid in diagnosis of the disease. (Cusabio offers monoclonal antibody and other types of antibodies. http://www.cusabio.com/)

#179201 Abnormalities in the synapses may trigger spinal muscular atrophy

Posted by whcaroline on 16 May 2017 - 09:04 AM in Immunology Products

A study from Columbia University demonstrates that spinal muscular atrophy is partly caused by abnormalities in the synapses that connect sensory neurons and motor neurons. The finding extends our knowledge of this devastating disease.
Spinal muscular atrophy (SMA) is a rare, genetic disorder that affects the control of muscle movement. Mutations in the SMN1, UBA1, DYNC1H1, and VAPB genes have been linked to the disease. Most cases of SMA are caused by a genetic defect in the SMN1 gene. To date, at least 65 mutations in the SMN1 gene have been found to cause spinal muscular atrophy. SMN1 provides instructions for making the SMN protein, which is widely expressed in all animal cells and plays a key role in transcriptional regulation, telomerase regeneration, and cellular trafficking. A lack of SMN protein, most often due to genetic mutations in SMN1, leads to the inefficient assembly of the machinery needed to process pre-mRNA. Motor neurons are vulnerable to SMN deficiency and die prematurely. The loss of motor neurons leads to atrophy of muscles used for controlling movement. (Cusabio offers proteins and antibodies. http://www.cusabio.com/)
With this knowledge, scientists have long hypothesized that restoring the diseased neurons may treat the disease. However, this approach did not work well in SMA mouse model, indicating that the disease may also involve other cells.
The new study is built on previous research. Dr George Mentis, who led the new study, previously discovered that abnormalities in the synapses between sensory neurons and spinal motor neurons seem to contribute to SMA development before the death of motor neurons. In this work, Mentis' team demonstrated in SMA mouse model that SMN shortage in sensory neurons changed the synapses that connect them to motor neurons, leading to a reduction in the release of glutamate, a key neurotransmitter involved in neural activation, which in turn decreased the expression of the potassium channel Kv2.1 at the surface of motor neurons. Reduced Kv2.1 expression affects the function of motor neurons and their control on muscles. The researchers noted that “a reduction in proprioceptive synaptic drive leads to motor neuron dysfunction and motor behavior impairments.”
The researchers also found that increasing neuronal activity pharmacologically almost normalized Kv2.1 expression and improved motor function. Based on these results, the researchers believed that abnormalities in sensory synapses contribute to SMA development. Therefore, increasing synaptic activity might be a way to treat SMA.
The study “Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy” appears in Nature Neuroscience.

#179187 SIRT6 deficiency may contribute to neurodegeneration

Posted by whcaroline on 09 May 2017 - 11:04 AM in Immunology Products

Published in Cell Reports on March 28, 2017, a study identifies that a protein crucial for DNA repair protects the brain from neurodegeneration, a finding that could have significant implications in the treatment of neurodegenerative disorders like Alzheimer's disease (AD).
Aging is considered a result of DNA damage accumulation. Both normal metabolic activities and environmental factors can cause DNA damage in human cells. Human cells employ multiple DNA repair mechanisms to monitor and repair damaged DNA. When these repair mechanisms fail to work, unrepaired DNA damages may accumulate in the cell and impair its normal function.
The accumulation of DNA damage is particularly dangerous in the brain. There is evidence that DNA damage accumulation is even higher in the brains of patients with neurodegenerative disorders. But the underlying mechanism remains unclear. 
Recently, a team of researchers from the Ben-Gurion University of the Negev, Harvard Medical School, and the University of Leipzig found that a protein called SIRT6 is a key component of the DNA repair process. Using mice lacking SIRT6, they demonstrated that high SIRT6 levels promote DNA repair whereas low SIRT6 levels enable DNA damage accumulation.
SIRT6 belongs to the Sirtuin protein family, which has been linked with many cellular processes, such as aging, transcription, glycolysis, apoptosis, and inflammation. Mammals possess seven sirtuins (SIRT1-7). Lack of SIRT6 leads to genomic instability, premature aging, and death in mice. In contrast, mice that produce more SIRT6 protein exhibits an extended maximum lifespan. Aging rats have decreased levels of SIRT6 in their brains. At the molecular level, SIRT6 recruits molecules critical for proper DNA repair to the DNA damage sites. Cells lacking SIRT6 fail to repair DNA damage.
To determine the relationship between SIRT6, DNA damage accumulation, and neurodegeneration, the researchers created a brain-specific SIRT6-knockout mouse model. The brains of the mice exhibited pathological marks associated with DNA damage and neurodegeneration, and the mice developed behavioral defects. SIRT6 depletion in cells led to increased tau stability and apoptosis. Additionally, cells lacking SIRT6 were more sensitive to genotoxic insults.
Next, the researchers measured the levels of SIRT6 in sporadic AD brain samples and analyzed normal brain gene expression. Results showed that the protein is highly expressed in normal human brains but is significantly decreased in AD patients.
In summary, the study suggests that SIRT6 protects the brain from DNA damage accumulation and neurodegeneration, and SIRT6 loss can result in toxic Tau stability and phosphorylation. So targeting SIRT6 or its downstream signaling could be a potential therapeutic strategy for AD and age-related neurodegeneration.
Researchers participating in the study include Shai Kaluski, Miguel Portillo, Antoine Besnard, Daniel Stein, Monica Einav, Lei Zhong, Uwe Ueberham, Thomas Arendt, Raul Mostoslavsky, Amar Sahay, Debra Toiber, and Debra Toiber. (SIRT6 protein and other proteins can be offered by Cusabio.)

#179180 Scientists use multiple methods to examine HIV-1-antibody interactions

Posted by whcaroline on 05 May 2017 - 06:01 AM in Immunology Products

Using experimental and mathematical methods, scientists from the US and Switzerland have identified interactions between the virus HIV-1 and antibodies. These interactions can be utilized to prevent the deadly virus from spreading from person to person.
The study, titled “Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters,” is published online May 4, 2017 in the journal PLoS Pathogens. Study authors include Oliver Brandenberg at California Institute of Technology, Carsten Magnus and Roland Regoes at ETH Zurich, and Peter Rusert, Huldrych Günthard, and Alexandra Trkola at the University of Zürich.
Broadly neutralizing antibodies (bNAbs) are neutralizing antibodies which neutralize multiple HIV-1 viral strains. The potent effect of bNAbs that target the HIV-1 envelope glycoprotein trimer (Env) has opened a new avenue for therapies and vaccines. Unfortunately, the implementation of these antibodies is impeded by multiple questions. If we can better understand HIV-antibody interactions and the mucosal transmission process, it may accelerate the development of HIV management strategies.
The researchers started by studying how many neutralizing antibodies (nAbs) are required to neutralize each HIV-1 envolop HIV-1 Env trimer. Next, they looked into the mechanism of mucosal HIV-1 transmission. Finally, they used all previously determined parameters to model human HIV-1 sexual transmission.
The researchers noted that their study represents a useful tool to enhance our knowledge of virus-antibody interactions and viral mucosal transmission and may lay the foundation for future development of HIV-antibody-based therapies and vaccines.  (Cusabio offers various antibodies.

#179178 Existing drugs may be repurposed to treat asthma

Posted by whcaroline on 03 May 2017 - 08:33 AM in Immunology Products

A team of researchers from Imperial College London, University of Liège, and several other institutes have a novel pathway within the immune system that triggers an asthma attack. The study, “Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation,” appears in the journal Nature Medicine. Marie Toussaint is the first author.
Asthma is one of the most common inflammatory diseases of the airways and its incidence is increasing throughout the world. It is estimated that 10% of adults in developed countries have asthma, and the morbility of asthma is even higher. For example, in the US alone, over 25 million people suffer from asthma, and approximately 7 million of them are children.
Asthma is characterized by recurring periods of wheezing, shortness of breath, reversible airflow obstruction, and bronchospasm. Severity of the disease varies among patients. Sometimes, asthma can be life-threatening, so an appropriate treatment is essential. Asthma is a result of interaction between genetic and environmental effects. Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Some studies have linked amplification of the type-2 immune response to asthma excerbation. However, the precise mechanism of how virus infection promotes type-2 immune response remains elusive.
Now the new study reveals a novel pathway involved in asthma. Existing drugs are available to inhibit this pathway. These drugs may be repurposed to treat asthma.
Our bodies have two types of immune responses: type 1 responds to viruses and type 2 responds to allergens. In theory, activation of one should inhibit the other. However in fact, people who get a cold have increased risk of having an asthma attack. In this work, the researchers examined nasal samples from people with asthma and healthy volunteers. Results showed that asthma patients had elevated levels of proteins associated with type 2 immune response after rhinovirus infection. Moreover, they also had higher levels of host dsDNA.
Using a mouse model of allergic airway hypersensitivity, they researchers found that rhinovirus infection triggers release of dsDNA by neutrophils, a type of while blood cells that form part of the innate immune system. Further experiments in mice showed that treatment with an enzyme that degrades DNA reduced type-2 immune response after rhinovirus infection, and resulted in decreased inflammation. The enzyme, called DNase, is already used to treat cystic fibrosis.
Taken together, the study shows that extracellular dsDNA may "contribute to the pathogenesis and may represent potential therapeutic targets of rhinovirus-induced asthma exacerbations."  (Cusabio offers various proteins and antibodies. http://www.cusabio.com/)

#179176 New insight into brain inflammation in neurological diseases

Posted by whcaroline on 01 May 2017 - 08:12 AM in Immunology Products

Neurological diseases, such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, multiple sclerosis, and stroke, involves brain inflammation. However, little is known about the mechanism of the inflammation. A new study, carried out by researchers including Leslie Freeman, Haitao Guo, Clément David, June Brickey, Sushmita Jha, and Jenny P.-Y. Ting at the University of North Carolina at Chapel Hill, has identified important molecules that trigger inflammation in the brain. Moreover, human patients with multiple sclerosis have large amounts of the same molecules in their brain. Thus, targeting these inflammatory molecules might be a way to treat multiple sclerosis. The study may also have profound implications in other neurological diseases.
In the study, Dr Jenny Ting and colleagues looked at lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination. They found that LPC triggers the inflammatory activation of mouse immune cells through two proteins called NLRP3 and NLRC4. Next, Ting's team used a mouse model of multiple sclerosis. In this model, mice received a chemical called cuprizone, leading to brain inflammation and demyelination. The researchers found that when mice did not have the two genes NLRC4 and NLRP3, the usual inflammatory activation of astrocytes and microglia was significantly decreased. The results suggest that NLRC4 and NLRP3 are involved in LPC-induced brain inflammation.
NLRC4 (NLR family CARD domain-containing protein 4) is best associated with causing the formation of the inflammasome, a multiproteinoligomerthat belongs to the innate immune system. NALP3 (NACHT, LRR and PYD domains-containing protein 3) is a component of the inflammasome that functions as a pathogen recognition receptor. The NLRC4 and NLRP3 proteins cause inflammation in response to certain microbes as well as non-microbial signals associated with tissue damage.
Study author Dr Haitao Guo noted that their study provides the first clear evidence that NLRC4 and NLRP3 play a key role in astrocytic and microglial inflammation, and LPC causes the inflammation. The study “NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes” was published 28 February 2017 in the Journal of Experimental Medicine. (NLRC4, NLRP3, and related antibodies can be offered by CusAb.)

#179167 New antibody may improve diagnosis of prostate cancer

Posted by whcaroline on 26 April 2017 - 09:34 AM in Immunology Products

New antibody may improve diagnosis of prostate cancer
Prostate cancer is the most frequently diagnosed malignancy in adult men in the developed world. Even if diagnosed and treated early, prostate cancer may progress to aggressive castrate-resistant prostate cancer. In fact, prostate cancer is the second leading cause of cancer-related death in men in certain countries. One reason that makes prostate cancer hard to treat is that prostate cancer is highly heterogeneous.
Recently, Roche announced that a monoclonal primary antibody, SP116, could improve the diagnosis of prostate cancer. This antibody recognizes certain parts of the protein AMACR. AMACR, or alpha-methylacyl-CoA racemase, is an enzyme that is found in mitochondria and peroxisomes in cells. In peroxisomes, AMACR is involved in the breakdown of a fatty acid called pristanic acid; in mitochondria, AMACR further breaks down the molecules derived from pristanic acid. Deficiency in AMACR may cause many  neurological problems. In prostate adenocarcinoma, AMACR is often elevated, making it a biomarker for the disease.
The new antibody SP116 is effective in diagnosing prostate cancer, when used in combination with the VENTANA Basal Cell Cocktail, which detects two proteins called 34ßE12 and p63. This new diagnostic approach requires less tissue samples in comparison with traditional methods. The SP116-VENTANA cocktail might improve diagnosis as well survival of prostate cancer.
Prostate cancer accounts for about 30% of all cancer diagnoses in American men. It is imperative to develop ways to reduce morbidity and mortality from the disease. (Cusabio offers polyclonal antibody.)

#179161 Lung epithelial cells produce a protective enzyme against chitin

Posted by whcaroline on 24 April 2017 - 10:34 AM in Immunology Products

Described in the prestigious journal Cell and led by Richard Locksley at the University of California, a newest study has revealed that lung epithelial cells produces an enzyme that protects the lungs from a common harmful compound, chitin.
Chitin is a nitrogen-containing polysaccharide that makes up the cell walls of fungi and the exoskeletons of insects and crustaceans. Moreover, other organisms such as molluscs, cephalopods, and fish can also produce chitin. Some of these chitin producing organisms are pathogens in other species.
Chitin is one of the toughest natural materials and exists widely in the environment. Each time you take a breath, you may inhale bits of debris rich in chitin. There is evidence that mammalian exposure to chitin is related to upregulation and downregulation of inflammatory responses, including those involved in asthma.
It is well established that chitin is degraded and recycled by ubiquitous bacterial and fungal chitinases, which are hydrolytic enzymes. Vertebrates also express chitinases, but little is known about their role in mammalian physiology. For the current study, the team looked at mammalian chitinases and found that distinct lung epithelial cells secrete acidic mammalian chitinase (AMCase).
Locksley and the team created genetically modified mice that do not produce AMCase. These AMCase-deficient mice showed premature morbidity and mortality, in comparison with the control mice. Moreover, the lungs of the AMCase-deficient mice showed the accumulation of chitin in the airways, absorbed less oxygen than normal, and exhibited signs of inflammation and fibrosis. These symptoms were decreased by restoration of lung chitinase activity by genetic or therapeutic approaches.
Next, the researchers analyzed samples of airway fluid from patients with interstitial lung disease. The measurement of chitin showed that these patients had much more chitin in their airways than healthy people. But these patients did not lack AMCase. Why this occurs requires further research.
Taken together, “These data suggest that altered chitin clearance could exacerbate fibrogenic pathways in the setting of lung diseases characterized by epithelial cell dysfunction.”
Other researchers of the study include Steven Van Dyken, Hong-Erh Liang, Ram Naikawadi, Prescott Woodruff, Paul Wolters, and David Erle. (Cusabio offers AMCase and antibody.)

#179157 Frog protein fights against flu virus

Posted by whcaroline on 20 April 2017 - 10:19 AM in Immunology Products

To find novel antiviral durgs, investigators have studied proteins that animals produce to protect them from pathogens for a long period of time. Evidence shows that proteins in amphibian secretions have the ability to fight off certian viruses such as HIV and herpes.
Now a newest study reveals that a frog slime protein can kill flu virus. The study, published in Immunity and led by Joshy Jacob from Emory University, reports that a peptide from the skin of the South Indian frog, named "urumin", is virucidal for the H1 variety of influenza viruses.
Unlike humans, frogs do not have an immune system that protects them against pathogens. But the skins of frog are known to secrete host defense peptides, which possess broad antimicrobial function and help protect them. To determine if these peptides could help combat flu, Jacob's collected mucus from the skin of 15 frogs after mild electrical stimulation.
They screened 32 peptides in the mucus and identified four that had anti-flu properties. One peptide, which they named "urumin", in particular grabbed their attention. Urumin effectively destroyed several strains of influenza viruses and some harmful microbes.
With the help of electron microscope, they demonstrated that urumin specifically targeted the stalk of H1 hemagglutinin and physically destroyed influenza virions. The stalk of H1 hemagglutinin is a conserved region of the flu virus, and this region is also the target of antibodies induced by universal flu vaccines. The finding might aid in developing new anti-influenza molecules targeting conserved components on the virus.
Animal experiments demonstrated the protective effect of urumin against lethal flu infection. Importantly, the peptide could kill drug-resistant H1 influenza viruses. Overall, the data suggests that urumin represents a new class of antiviral agent. 
Vaccines and antiviral drugs are both important weapons in the fight against harmful viruses. But during pandemics, there may not be enough time to produce vaccines, so antiviral drugs become the first line of defense. It is important to develop new antiviral drugs because of the possible emergence of drug resistance.
In addition to Emory University, Rajiv Gandhi Center for Biotechnology in India, and Icahn School of Medicine at Mount Sinai also participate in the study.  (Cusabio offers proteins and antibodies. http://www.cusabio.com/)

#179153 New insight into neutrophil-mediated autoimmune vasculitis

Posted by whcaroline on 18 April 2017 - 08:57 AM in Immunology Products

Neutrophils, or called neutrocytes, are a type of white blood cells that help combat infections by bacteria, viruses, or other organisms. These cells travel to the site of infection when a pathogen invades the body, and they contain toxic chemicals that can effectively kill the pathogen. However, under certain conditions, neutrophils can also cause autoimmune diseaseas. For example, inappropriate activation of neutrophils plays a pathological role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Previous studies have implicated EMA4D (a protein that regulates immune responses) in autoimmunity. However, so fat the role of EMA4D in AAV remains elusive.
According to a study published Annals of the Rheumatic Diseases, the SEMA4D protein normally inhibits neutrophil activation. In AAV, however, the inhibition is broken down, triggering inflammation and disease. These results suggest that SEMA4D could be a biomarker and therapeutic target for AAV. The study is led by researchers from Osaka University Graduate School of Medicine, World Premier International Immunology Frontier Research Center, and AMED–CREST in Japan.
To identify the functions of SEMA4D in neutrophil activation AAV pathogenesis, the team examined blood samples from patients with AAV and healthy individuals, and wild-type and SEMA4D -/- mice neutrophils. They found that blood levels of SEMA4D were increased in AAV patients and were associated with disease activity scores. Moreover, cell-surface expression of SEMA4D was decreased in neutrophils from AAV patients. The researchers concluded that "SEMA4D has potential as a serological marker of AAV, and represents a promising therapeutic target for clinical management of neutrophil-mediated autoimmune vasculitis."  (Cusabio provides EMA4D related proteins and antibodies.)

#179150 Excessive Id1 protein may increase the risk of obesity

Posted by whcaroline on 16 April 2017 - 08:37 AM in Immunology Products

A study appearing in Diabetes shows that excessive expression of a protein called inhibitor of differentiation 1 (Id1) seems to increase the risk of obesity and possibly obesity-related diseases. The study is carried out by Augusta University researchers.
Id1 is a member of the basic HLH family of transcription factors. This protein is known to promote proliferation and inhibit differentiation. Upregulation of Id1 expression has been found in a variety of cancers, such as prostate cancer, glioblastoma, and non-small cell lung cancer.
The new study reveals a new function of Id1: Excessive Id1 reduces fat burning ability of brown fat. Discovery of Id1 as a regulator of brown fat metabolism may open an avenue for therapeutic intervention for obesity and diabetes.
In the work, the team created mice that expressed high levels of Id1 in the fat cells. These mice gained much more weight than the control mice, no matter both groups of mice were on a high-fat diet or on a normal diet. Further investigation demonstrated that the protein Id1 directly binds to and suppresses the activity of PGC1α, a transcriptional coactivator involved in regulation of energy metabolism, and therefore reduces brown fat’s burning ability.
Fat, or adipose tissue, is a kind of body tissue that helps store energy and serves as a source of energy. There are two major types of fat -- brown and white. Brown fat helps turn food into body heat, so it is also referred to as “good” fat. White fat, or called “bad” fat, stores energy from food and makes people fatter.
The finding that the Id1 protein inhibits brown fat's burning ability explains why mice with high Id1 levels were more likely to develop obesity. It is well established that obesity is a risk factor of many health problems, including diabetes, heart disease, and high blood pressure. The study “has significant implications in the treatment of obesity and its associated diseases such as diabetes.” (Cusabio provides proteins and antibodies. http://www.cusabio.c...talog-20-1.html)

#179142 Potential therapeutic strategy for rhabdoid tumors

Posted by whcaroline on 12 April 2017 - 08:33 AM in Immunology Products

A paper “A functional screening of the kinome identifies the Polo-like kinase 4 as a potential therapeutic target for malignant rhabdoid tumors, and possibly, other embryonal tumors of the brain”, which is published in the journal Pediatric Blood & Cancer, identifies a protein kinase as a therapeutic target for rhabdoid tumors.
Malignant rhabdoid tumor is a rare, aggressive tumor that mainly affects infants and toddlers. The tumor usually arises in the kidney but can also arise in other parts of the body such as the brain. Prognosis of patients with malignant rhabdoid tumor is extremely poor that they may die within weeks of being diagnosed. Existing drugs are limited in their therapeutic effect. In this scenario, more effective treatments are in urgent need.
Protein kinases are a group of enzymes that modifies other proteins by adding phosphate groups to them. These enzymes regulate essential aspects of cell function, and mutations and dysregulation of them may cause human disease, including cancer. In this work, the researchers set out to identify kinases associated with rhabdoid tumors.
Using an advanced gene editing technique called CRISPR/Cas9, the team individually mutated 160 kinases in a rhabdoid tumor cell line and monitored these cells. By doing so, they found that the Polo-like kinase 4 (PLK4) most significantly impaired rhabdoid tumor cell growth. PLK4 CRISPR-mutated rhabdoid cells showed a great decrease in proliferation, viability, and survival. Further investigation demonstrated that PLK4 expression is upregulated in rhabdoid tumors and additional embryonal brain tumors.
Based on the findings, the researchers hypothesized that targeting PLK4 with inhibitors might be a way to inhibit rhabdoid tumor growth. They tested a potent PLK4 inhibitor called CFI-4000945 in multiple rhabdoid tumor cell lines, and found that treatment with the inhibitor resulted in significant decrease in cell proliferation, survival, migration, and invasion. On the other hand, experiments in zebrafish showed that CFI-400945 did not harm normal development, suggesting that CFI-400945 might be safe for children. (PLK4 and other molecules like can be offered by Cusabio. http://www.cusabio.com/)
The study is conducted by investigators from Ann and Robert H. Lurie Children's Hospital of Chicago, Stanley Manne Children's Research Institute, Northwestern University, Thermo Fisher Scientific, and Juntendo University.

#179138 Antibody against CTGF protects against radiotherapy-associated fibrosis

Posted by whcaroline on 10 April 2017 - 08:36 AM in Immunology Products

An antibody provides great protection against radiation-induced pulmonary fibrosis, researchers report in Journal of the National Cancer Institute. The study is a collaboration of the German Cancer Research Center, University Hospital Center, and FibroGen, Inc.. (Cusabio provides various proteins and antibodies. http://www.cusabio.com/)
Radiotherapy is an important treatment option for patients with cancer. In fact, nearly two thirds of cancer patients will receive radiotherapy. For this, radiotherapy often claimed to be orthodox medicine’s number 1 weapon against cancer. In most cases, radiotherapy is effective and well tolerated. However, it has potential side-effects. For example, prolonged exposure to radiation causes the healthy tissue to inflame and eventually scar, a process called fibrosis.
Fibrosis is the development of fibrous connective tissue in response to injury or damage. Many growth factors and inflammation-promoting chemical messengers have been implicated in this process but there is still a lack of effective drugs that target these molecules to prevent or control pulmonary fibrosis. Once developed, fibrosis can be difficult to reverse.
The aim of this study is to find new targets for pulmonary fibrosis. The tested an antibody against the connective tissue growth factor (CTGF). Mice received the antibody before and after radiation therapy. The majority of the mice were protected from fibrosis, and the antibody treatment even reversed the fibrotic transformation in some mice. In comparison to control mice, mice receiving the antibody had reduced fibrosis symptoms, better health, and prolonged survival. When antibody treatment started 20 days after radiotherapy, 75% of the treated mice were able to survive a extremely high, potentially lethal dose of radiation. These data suggest that antibody to CTGF might have significant therapeutic effect against radiotherapy-induced pulmonary fibrosis. Now, the team is investigating whether the antibody could be effective against other forms of fibrotic disease.

#179129 Monoclonal antibody protects against two lethal viruses

Posted by whcaroline on 06 April 2017 - 06:16 AM in Immunology Products

A study reported in the journal Science Translational Medicine has found that a monoclonal antibody provides significant protection against two members of a virus family of Filoviridae -- Marburg and Ravn viruses.
Like some other viruses that belong to the virus family of Filoviridae, Marburg and Ravn viruses can cause hemorrhagic fever in human beings with high morbidity rates. For the present study, the team, led by researchers from the University of Texas Medical Branch, Vanderbilt University Medical Center, University of Natural Resources and Life Sciences, and Mapp Biopharmaceutical Inc., evaluated the ability of previously identified human monoclonal antibodies to protect guinea pigs from lethal infection. In further experiments, one of these antibodies, MR191-N, was given to nonhuman primates five days after Marburg or Ravn infection. Results showed that MR191-N attenuated symptoms, suggesting the antibody as a potential therapeutic agent for Marbur, Ravn and perhaps other filoviruses.
One of the most well known filoviruses, Ebola virus, becomes a big health concern. Marburg virus, which also belongs to the virus family of Filoviridae, is also very fatal: the mortality of Marburg infections is as high as 80%.
Monoclonal antibodies have emerged as an attractive option for many human diseases, especially autoimmune disorders and cancers. To date, over 45 monoclonal antibodies have been approved by the FDA and EMA.
This study demonstrated in rhesus macaques that the monoclonal antibody MR191-N protected all animals infected with Marburg or Ravn virus even when the antibody was administrated five days after the animals were exposed to the virus. This supports that monoclonal antibodies has the ability to protect against lethal viruses during advanced stages of disease. thus monoclonal antibodies may be a powerful weapon in the fight against virus outbreaks.
Marburg virus, the pathogen responsible for Marburg virus disease (MVD) (formerly known as Marburg haemorrhagic fever), poses a significant threat to human health. Its close cousin Ravn virus can also cause hemorrhagic fever in humans and nonhuman primates. (Cusabio provides various antibodies.)

#179127 Plasmapheresis may combat multi-drug resistant pathogen

Posted by whcaroline on 04 April 2017 - 06:20 AM in Immunology Products

Pseudomonas aeruginosa is a very common bacterium that can cause disease in both plants and animals. Pseudomonas aeruginosa is an opportunistic and naturally multi-drug resistant pathogen. For healthy people, the bacteria usually do not cause illness or only cause minor problems such as hot tub rash. More serious infections often occur in people in the hospital with another disease or people with a weakened immune system.
Bronchiectasis is a condition in which the airways of the lung are permanently damaged, widened, and thickened. Typical symptoms include chronic cough production, breathing difficulties, and recurrent infections. Bronchiectasis induces severe inflammation and tissue damage, making the lung more prone to further infections.
Pseudomonas aeruginosa is a main pathogen found in bronchiectasis patients, leading to increased morbidity and mortality. They researchers previously found that about 20% of patients with bronchiectasis and chronic Pseudomonas aeruginosa infection had excess IgG2 specific to the bacterial O-antigen. Unlike normal antibodies that protect the body against foreign materials, this IgG2 inhibited the immune system from killing the the Pseudomonas aeruginosa bacterium. Importantly, patients with the inhibitory antibody had more severe lung disease.
There is a hypothesis that removing the inhibitory antibody from the blood of patients might be a way to restore host immune killing and improve patient prognosis. Now a team led by researchers at the University of Birmingham finds that an approach called plasmapheresis can help remove these harmful antibodies.
In the new study, the researchers recruited two patients with bronchiectasis who had chronic Pseudomonas aeruginosa infections and failed to respond to antibiotic treatment, and used an approach called plasmapheresis to remove the inhibitory antibody from their blood. After treatment, both patients showed great improvement in health. Days in the hospital and antibiotic use dropped significantly. 
The results were encouraging and promising. Plasmapheresis is similar to kidney dialysis and is typically used to treat conditions in which harmful autoantibodies arise. This study suggests that plasmapheresis may help manage chronic Pseudomonas aeruginosa infections in bronchiectasis patients. The study appears in the American Journal of Respiratory and Critical Care Medicine. In addition, Cusabio offers various antibodies.

#179119 Researchers solve the structure of CFTR

Posted by whcaroline on 30 March 2017 - 06:55 AM in Immunology Products

Researchers have resolved the three-dimensional structure of the cystic fibrosis transmembrane conductance regulator (CFTR), according to a paper appearing in the journal Cell.

The CFTR protein, which is encoded by the CFTR gene, functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. It transports chloride ions into and out of cells. CFTR has been implicated in several human diseases, including cystic fibrosis. Cystic fibrosis is caused by the presence of mutations in both copies of CFTR gene. The mutated CFTR causes the body to produce abnormally thick and sticky mucus. This kind of mucus accumulates in various organs, mostly the lungs, causing tissue damage. Over time, cystic fibrosis can lead to difficulty breathing and frequent lung infections.

Cystic fibrosis has no cure. The primary goals of current treatment are to control lung infection and manage complications. To develop more specific treatments for the disease, a better understanding of CFTR s function is necessary. However, the human CFTR protein is unable to work well in the lab.

Given that a number of animals also have the protein, the researchers chose to study the zebrafish version of CFTR. They used zebrafish CFTR to map the location of disease-causing mutations. Using an imaging technique called cryo-electron microscopy, they revealed the detailed structure of both human and zebrafish CFTR, and found that under identical conditions human CFTR structure is very similar to zebrafish CFTR structure.

The structural data presented in the study would help understand CFTR function and how mutations in it can trigger cystic fibrosis. Although cystic fibrosis is a rare disease, affecting 70,000 people worldwide, it can seriously affect quality of life. Patients require long-term treatment, frequent hospitalization, and even lung transplant.

The study is carried out by Fangyu Liu, Zhe Zhang, David Gadsby, and Jue Chen from The Rockefeller University in collaboration with László Csanády from Semmelweis University. Besides, CFTR and other proteins and antibodies can be offered by CusAb. http://www.cusabio.com/

#179111 A genetic variant in PTPRD is linked with tauopathy

Posted by whcaroline on 28 March 2017 - 04:30 AM in Immunology Products

According to a study in Molecular Psychiatry, the protein tyrosine phosphatase receptor-type delta (PTPRD) gene is linked with tauopathy.
Neurofibrillary tangles (NFTs) -- aggregates of abnormally formed tau protein -- occur as part of the normal aging process. But in certain diseases such as Alzheimer's disease (AD), Lytico-Bodig disease, and Postencephalitic parkinsonism, the amounts of NFTs are far greater. These diseases are known as tauopathies.
It is believed that NFTs are a major contributor to cognitive decline in AD, but the precise mechanism of NFT formation is not fully understood. Now a team of researchers from Rush University Medical Center and the Brigham and Women's Hospital in Boston has found that a gene called PTPRD is associated with susceptibility to NFTs. The study's findings were published 21 March 2017 in the journal Molecular Psychiatry.
In the study, the team examined autopsies from 909 individuals and identified a genetic variant in the PTPRD gene that seemed to be associated with the accumulation of NFTs. The researchers the validated the finding in an independent data set of 369 autopsies.
According to study first author Lori Chibnik, this genetic variant is common: the majority of people have one or two copies of the version of the gene. Furthermore, the newly identified variant can influence multiple mechanisms of the formation of NFTs. “These analyses offer an evaluation of genetic susceptibility to NFT,” the researchers wrote in their paper. Study senior author De Jager noted the results need further validation. How PTPRD and the variant contribute to NFT accumulation is still a mystery.
Previous studies in animals have shown that PTPRD plays a role in memory dysfunction and worsening of Tau pathology. These studies and the new work indicate that manipulating PTPRD levels might be a way to decrease the burden of Tau pathology.
The PTPRD gene encodes an enzyme that is a member of the protein tyrosine phosphatase (PTP) family. PTPs modulate cell growth, differentiation, division, oncogenic transformation, and many other cellular activities.
Besides, PTPRD protein and antibody can be offered by CusAb. http://www.cusabio.com/

#179100 New tool may improve prognosis of rheumatoid arthritis

Posted by whcaroline on 26 March 2017 - 08:03 AM in Immunology Products

Rheumatoid arthritis (RA) is a long-term autoimmune disorder in which the body's immune system attacks joints on both sides of the body, causing inflammation, pain, swelling and loss of joint function. The disease affects everyone differently and treatments include medicine, lifestyle changes, and surgery. In RA, antibodies are produced that impact the inflammation in the joints.
In a paper in the Annals of Rheumatic Diseases, a team led by researchers from Uppsala University, Karolinska University Hospital and Karolinska Institutet, and Karolinska Institutet in Sweden has found that antibodies against the cartilage protein collagen II may help predict prognosis and choose therapy for RA. These antibodies seem to be linked with a good prognosis.
A certain percentage of RA patients have antibodies produced to collagen II, a structural protein that is the basis for articular cartilage and hyaline cartilage in the joint. These antibodies contribute to inflammation early in the disease but decrease over time.
The study enrolled a group of 773 RA patients from the Swedish Epidemiological Investigation in Rheumatoid Arthritis study. The team followed the patients for as long as five years. Using the method ELISA to measure the levels of antibodies against collagen II and citrullinated peptides, they identified that subjects who had collagen antibodies exhibited severer inflammation during the first six months after diagnosis, after this there was no difference compared to subjects who did not have collagen antibodies. In addition, subjects who had collagen antibodies at diagnosis were more likely to have better outcomes. In contrast, subjects with antibodies against citrullinated peptides had increased inflammation later in disease progression and tended to have worse outcomes.
RA is a multifactorial disease. Some patients have rheumatoid factor and/or anticitrullinated protein peptide autoantibodies while others do not. The study indicates that the combined analysis of antibodies against collagen II and citrullinated peptides "may be a new two-dimensional tool for predicting the prognosis and choosing therapy in newly diagnosed patients with RA." Johan Ronnelid from Department of Immunology, Genetics and Pathology of Uppsala University is the study leader.
By the way, Cusabio offers various antibodies such as polyclonal antibody.

#179094 Inhibition of GLO1 enzyme might be a way to treat depression

Posted by whcaroline on 22 March 2017 - 06:24 AM in Immunology Products

According to a study published in Molecular Psychiatry and led by researchers from the University of California San Diego School of Medicine, inhibiting an enzyme can alleviate symptoms of depression, providing a new therapeutic target for the disease.
As a common mood disorder, depression is estimated to affect 19 million people in the USA alone. People with depression experience overwhelming feelings of sadness, unpleasure, guilt and hopelessness, which interfere with daily life. Depression is major cause of disability and suicide worldwide.
Currently, more than one hundred depression medications, or antidepressants, are available, such a Prozac, Cymbalta, Zoloft and Lexapro. However, not everyone can benefit from these medications, and conventional antidepressants requires 2-4 weeks of continuous treatment to elicit their therapeutic effects. It is urgent to find fast-onset antidepressants.
Glyoxalase 1 (GLO1), also known as lactoylglutathione lyase, is an important enzyme that helps remove a byproduct of cell metabolism. This byproduct inhibits nerve cells and affects mood and behavior. Growing evidence shows that modulation of GLO1 activity can be a way to treat neurological and psychiatric conditions.
In the study, the researchers investigated three groups of mice: the first group that received the new treatment that blocks GLO1; the second group that received the conventional drug Prozac; and the third group that were left untreated. Results showed that inhibition of GLO1 reduced symptoms of depression in 5 days while Prozac took 14 days to show therapeutic effect. Collectively, the findings suggest that drugs that inhibit GLO1 may be used as fast-onset antidepressants.
Existing antidepressants can also cause other side effects, such as weight gain, nausea, and sleep disruption. It may takes years before the method used in this study can be tested in humans in clinical trails. But drugs that inhibit GLO1 may hold hope for a better treatment.
Besides, GLO1 protein and other bio-molecules can be offered by Cusabio, a biotech company specialized in manufacturing proteins and antibodies. http://www.cusabio.com/

#179089 SF3B1 may be a new target for certain melanomas

Posted by whcaroline on 20 March 2017 - 08:43 AM in Immunology Products

Study leads to ways to treat patients with IBD with low NLRP12 levels
A paper in Nature Immunity provides clues to mechanism of inflammatory bowel disease (IBD), a group of conditions that involve chronic immune response and inflammation of the gastrointestinal tract. Ulcerative colitis and Crohn disease are the two major types of IBD. It’s estimated that the prevalence for IBD is 396 cases per 100,000 persons annually. The increasing prevalence of IBD creates a considerable burden to individual patients, families as well as the health care system.
The new study is a collaboration of University of North Carolina, University of Michigan, Columbia University Medical Center, Tel-Aviv University, and Janssen Pharmaceuticals. It reveals that beneficial bacteria in the gut may be the key to treating IBD.
Although the exact cause of IBD is not clear, mounting evidence suggests that IBD is a result of the interaction of host genetics, the microbiome, and inflammatory responses. The findings of the new study support this concept.
The researchers previously found that a protein called NLRP12, which is a negative regulator of inflammatory signaling, suppresses inflammation in response to bacterial components, and that it provides protection against colitis, an inflammation of the colon, and colitis-related colon cancer.
For the current study, the researchers further explored the role of NLRP12 in IBD. By analyzing public data of human colitis patients, they noticed that the expression of NLRP12 is reduced in colitis. Experiments in mouse models showed that NLRP12 deficiency increased basal colonic inflammation, which disrupted the balance of the microbiome. NLRP12-deficient mice had less protective bacteria and more harmful bacteria in their gut, and were more susceptible to colitis compared to wide-type mice.
Importantly, the researchers found that these negative effects of NLRP12 deficiency could be reversed by the treatment with antibodies that target inflammatory cytokines or by the administration of beneficial bacteria that normally grow in the gut. Collectively, the results suggest a pivotal role for NLRP12 in keeping the microbiome in balance to prevent inflammation.
“These findings reveal a feed-forward loop in which NLRP12 promotes specific commensals that can reverse gut inflammation, while cytokine blockade during NLRP12 deficiency can reverse dysbiosis,” the researchers concluded. Cusabio offers NLRP12, and antibodies.  http://www.cusabio.com/

#179083 Anti-CD47 antibody could treat childhood brain tumors

Posted by whcaroline on 16 March 2017 - 09:27 AM in Immunology Products

An international research team consisting of researchers from the USA, Canada, Germany, and Switzerland has demonstrated that a humanized antibody that blocks the CD47 protein on tumor cells could treat a variety of pediatric brain tumors. In vitro and in vivo experiments demonstrate the safety and efficacy of the antibody.
The work is a collaboration of Stanford University School of Medicine, The Hospital for Sick Children, Heinrich-Heine-University Düsseldorf, Johns Hopkins University School of Medicine, and Oregon Health & Science University.
CD47 is a membrane protein that is involved in many cellular processes, such as proliferation, apoptosis, adhesion, and migration. Previous research has determined that CD47 is overexpressed in all cancer cells, making it an attractive target for drug design. In cancer, CD47 acts as a "don't eat me" signal -- it prevents the innate immune system macrophages from engulfing and killing the cancer cells. Blocking this "don't eat me" signal with therapeutics such as an antibody has been considered a potential way to combat diverse cancers.
Currently, anti-CD47 antibodies are already being tested in clinical trials in adults who have tumors outside the central nervous system. In the new study, researchers including Dr Samuel Cheshier from the Stanford University School of Medicine conducted experiments to evaluate the effectiveness of these antibodies on patient-derived xenograft models of five aggressive and etiologically distinct pediatric brain tumors.
Although dramatic improvements in survival have been achieved, the mortality of childhood malignant primary brain tumors is still high. For most childhood brain tumors, the cause remains unknown and the optimal treatment regimen has not been determined. Some patients receive toxic radiotherapy and chemotherapy that engender serious side effects. The antibodies tested in this study hold a big advantage over the traditional therapies: they effectively kill tumor cells without affecting normal cells.
The researchers found that all the five types of brain tumors expressed the CD47 "don't eat me" signal and an "eat me" signal known as CRT. In vitro experiments showed that treatment with a humanized anti-CD47 antibody called Hu5F9-G4 caused the cancer cells to be engulfed and killed by macrophages while sparing normal brain cells.
Hu5F9-G4 also demonstrated therapeutic efficacy in vivo in mice implanted with pediatric brain tumors. The antibody was able to cross the blood-brain barrier. Mice treated with the antibody had prolonged survival. By examining the animals' brain, the researchers found that macrophages got inside the tumors and that the antibody treatment did not completely eliminate all tumors. This leads to a concept that combining the antibody with another cancer therapy may optimize the therapeutic effect. 
The study appears in Science Translational Medicine. Cusabio offers antibodies and proteins. http://www.cusabio.com/

#179075 Early immunotherapy protects monkeys from a HIV-like virus

Posted by whcaroline on 14 March 2017 - 08:03 AM in Immunology Products

Early antibody treatment is able to suppress a HIV-like virus for a long period of time, according to the findings of a study published in Nature.
The study, led by researchers from National Institutes of Health, the University of Cologne, The Rockefeller University, the Beth Israel Deaconess Medical Center, and the Frederick National Laboratory for Cancer Research, reveals that treatment with two antibodies immediately after infection enables the immune system to control the virus for a long period of time.
Currently, several different types of HIV drugs are clinically used, such as nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, and integrase inhibitors. These drugs can reduce viral load and control infections, but cannot cure HIV infection. Once a patient stops taking medications, the virus can come roaring back, attacking the immune system.
Broadly neutralizing anti-HIV-1 antibodies (bNAbs) are antibodies that can neutralize multiple HIV-1 viral strains, and they are used to develop vaccines and treatments for HIV and other lentiviruses. However, administration of bNAbs to chronically infected animals inhibits virus replication only for a short period of time. The virus finally returns to pre-treatment levels and causes disease.
To develop more effective antibody therapy for HIV, the researchers conducted experiments in a macaque simian/human immunodeficiency virus (SHIV) model. They found that two bNAbs 3BNC117 and 10-1074, when given in combination, can induce long-lasting immunity to SHIV.
A total of 13 monkeys were exposed to the SHIV virus and then were treated with the antibody combination. The researchers found that the antibody combination suppressed the virus to levels near or below the limit of detection, and this effect lasted for nearly six months. When the antibodies were eliminated from the monkey’s bodies, the virus rebounded in most of the animals.
However, 5 to 22 months later, plasma virus loads declined to undetectable levels in 6 of the monkeys and remained suppressed for another 5 to 13 months. Moreover, 4 additional monkeys maintained extremely low viral loads and normal counts of CD4+ T cells for more than 2 years. Taken together, 10 of the 13 treated monkeys benefitted from the antibody combination. Passive immunotherapy during acute SHIV infection can induce potent T-cell immunity that durably suppresses virus replication. The study may provides a preventive and therapeutic strategy for HIV. By the way, CusAb offers Biotin conjugated antibody.

Home - About - Terms of Service - Privacy - Contact Us

©1999-2013 Protocol Online, All rights reserved.