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An antibody enhances drug delivery to tumors

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#1 whcaroline

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Posted 22 December 2016 - 08:50 AM

Doheon Lee and Gou Young Koh11 from Korea Advanced Institute of Science and Technology (KAIST) and other researchers have demonstrated the effectiveness of an antibody on glioma, lung carcinoma, and breast cancer. The antibody, called ABTAA, is more effective than another antibody, ABA. ABTAA normalizes tumor blood vessels, reduce tumor aggressiveness, and enhance drug delivery. Study's findings have been reported in Cancer Cell.
 
Tumor blood vessels are very different from healthy blood vessels. In healthy tissues, endothelial cells and pericytes help maintain the integrity of vessel walls as well as support blood flow. In an established tumor, these cells are fallen apart. As a result, the blood vessels become leaky, blood flow is restricted, and the tumor becomes hypoxic.
 
Hypoxia is a condition where the tissues do not get enough oxygen. In response to hypoxia, tumors change the microenvironment and become more invasive. So, eliminating hypoxia is thought to be a promising treatment strategy for cancer.
 
ABTAA is developed to target the protein Ang2 in endothelial cells. Ang2 is rarely detectable in the body but is increased during times of stress such as infections and tumors. It can circulate through the bloodstream and damage vascular cells.
 
Surprisingly, Koh's group found that the antibody also activates another protein on endothelial cells, known as Tie2. Activation of Tie2 helps reduce vessel instability.
 
Previous studies have shown that antibodies that only block Ang2 indeed delay tumor progression but fail to lessen hypoxia. Since ABTAA can both block Ang2 and activate Tie2, it may perform better in terms of cancer treatment. To evaluate its efficacy, Koh's group tested ABTAA in mouse models of glioma, lung carcinoma, and breast cancer. They also tested another antibody called ABA, which inhibits Ang2 but does not impact Tie2. Results showed that ABTAA is more effective than ABA in normalizing tumor vessels. ABTAA lessens hypoxia, acidosis, tumor growth, and metastasis. Moreover, the antibody alters the tumor environment, allowing immune cells and drugs to get into the tumors.
 
An earlier study had found that ABTAA mitigates sepsis by strengthening and protecting blood vessels. Sepsis is a condition in which the immune system overreacts to an infection, causing severe problems. In the condition, blood vessels are weakened, porous, and leaky, which may result in inflammation, organ damage, pulmonary edema and death. ABTAA restores blood vessel function and thus creates a stable environment, so that the body can more effectively fight the infection. These studies underscore the therapeutic effect of ABTAA. CusAb provides polyclonal antibody.






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