PHILADELPHIA--(BUSINESS WIRE)--Biothera is presenting new data today at the world’s largest meeting of cancer researchers that shows its investigational cancer immunotherapy drug Imprime PGG has the potential to initiate a coordinated anti-tumor response involving both the innate and adaptive immune systems.
“Cancer often creates a protective, immunosuppressive environment that enables it to avoid detection and destruction by the immune system,” said Jeremy Graff, Ph.D., Senior Vice President, Biothera Pharmaceutical Research. “Our new research demonstrates that Imprime PGG initiates a cascade of immune responses, including the maturation of dendritic cells, the repolarization of macrophages and expansion of cytotoxic T cells. These data suggest that Imprime PGG treatment orchestrates a shift in the tumor microenvironment that may enable the immune system to more effectively recognize and kill cancer cells.”
Biothera is presenting four scientific posters – including three late-breaking session posters – at the 2015 American Association for Cancer Research annual meeting this week. The data provide further insight into the therapeutic mechanism of action for Imprime PGG, a yeast-derived 1,3-1,6 β glucan that serves as a pathogen associated molecular pattern (PAMP).
PAMPs are naturally recognized by the innate immune system (neutrophils, monocytes, macrophages, dendritic cells) and elicit a coordinated immune response to an invading pathogen involving both innate and adaptive immune cells. As a PAMP, Imprime PGG also effectively evokes a coordinated immune response, binding to and priming innate immune effector cells to recognize and kill antibody-targeted cancer cells. This binding enables critical cross-talk between the innate immune effector cells and the adaptive immune system that drives cytotoxic T cell expansion and the production of anti-tumor cytokines.
“Many cancer immunotherapies focus only on the adaptive immune system,” said Dr. Graff. “Together, the studies presented at this year’s AACR meeting provide compelling evidence that Imprime PGG treatment triggers a more complete and more coordinated anti-tumor immune response resulting from activation of both innate and adaptive immune systems.”
Biothera’s AACR poster presentations are as follows:
- Imprime PGG modulates the function of monocyte-derived M2 macrophages and dendritic cells to drive T-cell expansion. Data show that Imprime PGG effectively modulates human monocyte-derived macrophages and dendritic cells to increase antigen presentation to adaptive immune cells, resulting in expansion of CD4+ and CD8+ T cells, as well as Th 1 polarization. The findings suggest the potential of combining Imprime PGG with therapies that relieve tumor-mediated T cell immunosuppression. Abstract #LB-225 will be presented from 1:00 pm – 5:00 pm today in Section 39. News release.
- 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. In this study, Biothera demonstrates that Imprime PGG has the potential to enhance the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors by eliciting immune responses that enhance PD-L1 expression on tumor cells and tumor-associated macrophages, while prompting T cell expansion and functionality, including production of the potent anti-tumor cytokine IFN-γ. Abstract #LB-228 will be presented from 1:00 pm – 5:00 pm today in Section 39. News release.
- Imprime PGG conjugated directly to protein enables cross-presentation of antigen that generates multifunctional cytotoxic T cells. This proof-of-concept study found that an Imprime PGG-protein conjugate induced antigen presentation by dendritic cells that resulted in a 100-fold expansion CD8+ T cells, as well as the production of cytokines IFN-γ, TNF-α and IL-2. Abstract #LB-236 will be presented from 1:00 pm – 5:00 pm today in Section 39. News release.
- Imprime PGG decreases regulatory T cell suppression and enhances T cell proliferation and differentiation revealing additional mechanisms for its anti-tumor activity. Biothera researchers demonstrated that plasma from Imprime PGG-treated whole blood reduced the ability of regulatory T cells to suppress CD4+ T cells. In addition, Imprime PGG enhanced the proliferation of CD4+ and CD8+ T cells. Production of the critical anti-tumor cytokine IFN-γ also increased, suggesting Imprime PGG may drive polarization of T cells to a Th1, anti-tumor phenotype. Abstract #5034 will be presented from 8:00 am – 12:00 pm tomorrow in section 11, poster board number 26.
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.