Replies to post #168817 on Avid Bioservices Inc (CDMO)

[war0001]

Speaking of NYAS. Why in the world is Dr. Bracken still touting the benefits of Bavi in mice? Have we not after all the years of clinical trials with Bavi seen this same benefit in humans?
Is Bavi capable of "significantly depleted M2-likeTAMs and MDSCs and increased the presence of M1-like TAMs and mature dendritic cells" in humans? Why have we not established this fact by now and using this as a talking point instead of mice?

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http://www.nyas.org/Events/Detail.aspx?cid=68cd1e1f-4ba3-4b30-b491-bdeac74b9651



Antibody-mediated Inhibition of Phosphatidylserine: A Novel Strategy for Immune Checkpoint Blockade
Rolf Brekken, UT Southwestern

Phosphatidylserine (PS) is a potent immunosuppressive lipid typically segregated to the inner leaflet of the plasma membrane. PS is externalized on tumor vasculature, tumor-derived exosomes, and tumor cells in the tumor microenvironment and externalization is enhanced by therapy. Externalized PS interacts with immune cells where it actively promotes expansion of myeloid derived suppressor cells (MDSCs) and M2-like tumor associated macrophages (TAMs), which drive immunosuppression and tumor progression. Bavituximab is a PS-targeting antibody that is being evaluated clinically in cancer patients. In preclinical studies, treatment of tumor-bearing mice with 2aG4 or mch1N11 (murine-versions of bavituximab) significantly depleted M2-likeTAMs and MDSCs and increased the presence of M1-like TAMs and mature dendritic cells. In addition, PS blockade shifted the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. Furthermore, in the immune-competent tumor models combination of standard of care therapy with PS blockade induced potent durable tumor-specific T-cell immunity and significantly improved tumor free long-term survival. These data suggest that externalized PS defines a global immune checkpoint in tumors and support that antibody-mediated PS blockade can reverse PS-mediated immune checkpoint suppression, revitalize innate and the adaptive immunity, and promote therapeutically effective anti-tumor immunity.