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Aethlon Medical (AEMD) Note: Cancer Immunotherapy Article, Introduction to Dr. Douglas Taylor
Date:10/24/2013

ector T cells. Treatment of activated T cells with anti-PD-L1 antibodies reduce T cell proliferation, which correlates with attenuated IL-2 secretion.  In vitro cytotoxicity studies and in vivo growth inhibition can be restored utilizing anti-PD-L1 antibodies or by genetic silencing of PD-1. The expression of PD-L1 on tumor cells inhibits anti-tumor immunity through engagement of PD-1 on effector T cells. Expression of PD-L1 on tumors is correlated with reduced survival in many tumor types.

Due to the role of these molecules in immune regulation and correlation with cancer outcomes, these pathways are being targeted for immunotherapy. Bristol Myers' experimental PD-1 inhibitor Nivolumab and Merck's candidate, MK-3475, block the PD-1/PD-L1 interaction, allowing the immune system to react with the tumor cells. Yervoy targets a similar checkpoint, inhibiting the CTLA-4 pathway. Unlike genetically targeted drugs, which disrupt mutations that fuel tumor growth, the new agents treat the immune system. Current interest in targeting these molecular pathways raises a concern that their normal function acts as to modulate the immune system to prevent attacks on healthy cells. Studies in murine models deficient for PD-1 developed dilated cardiomyopathy and congestive heart failure and that expression of PD-1 may also prevent autoimmune diseases. Based on the critical role of PD-1 and CTLA-4, targeting their expression may be problematic resulting in serious side effects on the host. However, an essential component of the activity of such molecules may be due to their presence on exosomes released by tumor cells. We previously demonstrated the presence of these immunoregulatory molecules on tumor-derived exosomes and their ability to suppress T cell activation and proliferation (Taylor et al. Clinical Cancer Research, 9: 5113-5119, 2003). Thus, a reasonable approach that does not result in systemic toxicity would be the removal of these immunoregulatory
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