NorthWest Biotherapeutics Inc (NWBO)

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Remember PLX-3397 synergy with DCVax?

Why yes I do. Courtesy of Dr. Robert Prins.

Our new preliminary data strongly suggests that active immunotherapy with DC vaccination may create a pro-inflammatory tumor microenvironment that induces the immigration of immunosuppressive antigen presenting cells (iAPC), which express high levels of PD-L1 and IL-10. We show that these cells are phenotypically similar to the iAPC that dominantly influence the T-cell response to chronic viral infection, and may act to counteract effective T-cell responses induced by DC vaccination via a mechanism involving PDL1/PD-1. Furthermore, inhibition of iAPC using an anti-PD1 mAb (Nivolumab, BMS) OR a CNS penetrant inhibitor of CSF-1R (PLX-3397, Plexxikon), in conjunction with tumor lysate-pusled DC vaccination (DC-Vax-L), resulted in significantly prolonged survival in tumor-bearing animals with well-established intracranial (i.c.) gliomas. We therefore postulate that clinically relevant anti-tumor immunity to glioblastoma (GBM) must have two cellular components: 1) significant infiltration of tumor-specific tumor-infiltrating lymphocytes (TIL); and 2) blockade of immune-regulatory antigen presenting cell (iAPC) function within the tumor microenvironment. As such, our hypothesis is that the local cellular interactions between iAPC and T lymphocytes within the brain tumor microenvironment is a critical factor influencing the efficacy of immunotherapies in glioblastoma patients. A better understanding of the biology of these cellular interactions will provide insight into more effective ways to induce therapeutic anti-tumor immune responses for this deadly type of brain tumor.
grantome.com/grant/NIH/P50-CA211015-01A1-5383