On April 18, 2016 Biothera Pharmaceuticals, Inc. reported research providing new insights into the ability of the Company’s Phase 2 cancer immunotherapy to coordinate innate and adaptive immune responses and enhance the effectiveness of combination therapies (Press release, Biothera, APR 18, 2016, View Source [SID:1234511022]). The findings were presented today at the AACR (Free AACR Whitepaper) annual meeting, which is taking place in New Orleans, LA, April 16-20, 2016.
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AACR logoThe company is presenting five poster presentations at the AACR (Free AACR Whitepaper) meeting focusing on the unique therapeutic mechanisms of action for Imprime PGG, a Pathogen Associated Molecular Patterning molecule, or PAMP. Imprime PGG acts as an immunological "ignition switch" enlisting the innate immune system to enhance the therapeutic efficacy of tumor targeting, anti-angiogenic, and immune checkpoint inhibitor antibodies.
"These data provide compelling new evidence demonstrating in vivo that Imprime PGG can re-orient the immunosuppressive tumor microenvironment, especially in concert with anti-VEGF or anti-VEGF2 antibodies," said Jeremy Graff, Ph.D., Chief Scientific Officer and Senior Vice President, Research, at Biothera Pharmaceuticals. "Imprime PGG also effectively binds to dendritic cells, enhancing the maturation of these professional antigen presenting cells, which is key to enabling robust T cell-mediated anti-cancer immune responses and to driving therapeutic synergy with immune checkpoint inhibitors."
The Biothera Pharmaceuticals presentations, including three appearing in the late-breaking immunology research poster session, advance understanding of the mechanisms by which Imprime PGG augments immune responses:
Imprime PGG significantly enhances the efficacy of both anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors in preclinical in vivo Fully 83% of mice treated with Imprime PGG and anti-PD-L1 antibody were tumor-free after 29 days, compared with 33% of mice treated with anti-PD-L1 antibody alone. The tumor-free mice were re-injected in the opposite flank with cancer cells and remained tumor-free, indicating the establishment of immunological memory against the tumor.
Imprime PGG also upregulates expression of the critical co-stimulatory marker CD86, as well as PD-L1, on peripheral blood mononuclear cells (PBMCs) isolated from the blood of Imprime PGG-treated colon cancer patients, providing the first evidence from human clinical trials that Imprime elicits the critical immune changes in humans previously recognized in preclinical studies.
Additionally, Imprime PGG has been shown to trigger the direct tumor-killing functions of the innate immune system, dramatically reducing metastatic burden in concert with a tumor-targeting antibody in a model of melanoma metastases to lung.
By promoting myeloid-derived suppressor cell (MDSC) differentiation and repolarization of suppressive M2 macrophages, Imprime PGG re-educates the immune microenvironment and enhances the therapeutic efficacy of anti-angiogenic antibodies.
Further, Imprime PGG enables the activation and maturation of dendritic cells – the body’s professional antigen presenting cells – to facilitate T cell-mediated, antigen-specific immune responses.
The posters will be available on the Biothera Pharmaceuticals website, as they are presented today and tomorrow.