PHILADELPHIA--(BUSINESS WIRE)--A scientific poster presented today during a late-breaking session at the American Association for Cancer Research (AACR) annual meeting showed that Biothera’s Imprime PGG investigational cancer immunotherapy may have the potential to enhance the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors.
A growing body of evidence suggests that tumors actively evade destruction by cytotoxic T cells in part by upregulating cell surface expression of PD-L1. This immunomodulatory protein interacts with the PD-1 protein on the surface of T cells to, in effect, instruct T cells to ignore the tumor. Antibody therapies designed to disrupt this PD-1/PD-L1 interaction—i.e. the immune checkpoint inhibitors—can re-awaken the T cell attack on tumor cells and show great promise for treating a wide array of cancers, including malignant melanomas, renal cell carcinomas and non-small cell lung cancer. Translational studies from checkpoint inhibitor clinical trials have demonstrated the critical nature of PD-L1 expression on the surface of tumor cells and infiltrating macrophages.
“Previous studies suggest that the efficacy of anti-PD-1/PD-L1 immunotherapies could be enhanced if combined with agents that induce PD-L1 expression on the surface of tumor cells,” said Jeremy Graff, Ph.D., Senior Vice President, Biothera Pharmaceutical Research. “Our data show that Imprime PGG has the potential to elicit immune responses that drive enhanced PD-L1 expression on tumor cells as well as macrophages.”
In the study, macrophages and dendritic cells derived from Imprime PGG-treated monocytes in vitro exhibited increased surface expression of PD-L1. Importantly, Imprime PGG treatment also enhanced dendritic cell maturation and macrophage function, enabling both cell types to trigger expansion of CD4+ and CD8+ T cells and the production of the potent anti-tumor cytokine IFN-γ. Cell culture media derived from co-cultures of T cells with either macrophages or dendritic cells treated with Imprime PGG elicited a profound increase in expression of PD-L1 on the surface of tumor cells from a variety of tumor types (e.g. non-small cell lung cancer, breast cancer, pancreatic cancer).
“The upregulation of PD-L1 expression induced by Imprime PGG treatment on both the immune and tumor cells makes Imprime PGG a promising combination partner for the checkpoint inhibitor cancer immunotherapies,” said Dr. Graff.
Biothera’s research (Abstract #LB-228) is one of three late-breaking poster presentations the company will present from 1:00 pm – 5:00 pm today in Section 39 at the Pennsylvania Convention Center. The presentation is entitled, “Imprime PGG treatment elicits a coordinated antitumor immune response that triggers enhanced expression of PD-L1 on tumor cells as well as monocyte-derived macrophages and dendritic cells.”
Biothera is a privately held biotechnology company developing Imprime PGG, a late clinical stage immunotherapeutic drug candidate that modulates key immune cells to recognize and kill cancer. Proof of concept has been established from randomized and single-arm Phase 2 studies in non-small cell lung cancer (NSCLC), colorectal cancer, and chronic lymphocytic leukemia. In the NSCLC study, which evaluated the addition of Imprime PGG to bevacizumab and carboplatin/paclitaxel versus bevacizumab and chemotherapy alone, objective response rate was 60.4% versus 43.5%, duration of response was 10.3 months versus 5.6 months and median overall survival was 16.1 months versus 11.6 months. Studies are ongoing in metastatic colorectal cancer, pancreatic cancer and non-Hodgkin lymphoma. In addition, new research shows that Imprime PGG elicits a coordinated immune response that involves both innate and adaptive immunity.