PHILADELPHIA--(BUSINESS WIRE)--New research demonstrates that Imprime PGG, an investigational cancer immunotherapy drug in late-stage development by Biothera, modulates the function of key cells of the innate immune system—macrophages and dendritic cells—to drive expansion of T cells, which are critical for anti-cancer immunity. The results were reported today during a late-breaking scientific poster session at the American Association for Cancer Research annual meeting.
Significantly, the study demonstrated that Imprime PGG treatment effectively primes human monocyte-derived macrophages and dendritic cells to increase the number of both CD4+ and CD8+ T cells, and drive Th 1 polarization. CD4+ T cells are essential in regulating and directing immune responses, while CD8+ T cells directly attack and destroy tumor cells.
“These results further expand our understanding of Imprime PGG’s mechanism of action,” said Jeremy Graff, Ph.D., Senior Vice President, Biothera Pharmaceutical Research. “Most cancer immunotherapies are limited to targeting the adaptive immune system. Imprime PGG treatment, however, orchestrates a broader, more coordinated immune attack involving both the innate and adaptive immune systems.”
A yeast-derived 1,3-1,6 β glucan, Imprime PGG is a pathogen associated molecular pattern (PAMP). PAMPs are naturally recognized by the innate immune system (neutrophils, monocytes, macrophages, dendritic cells) and trigger a coordinated immune response to an invading pathogen involving both innate and adaptive immune cells. As a PAMP, Imprime PGG also effectively elicits a coordinated immune response, binding to and priming innate immune effector cells to recognize and kill antibody-targeted cancer cells and to enable critical cross-talk with the adaptive immune system.
The study reported today focused on the phenotypic and functional effects of Imprime PGG treatment on monocyte-derived macrophages and dendritic cells (MoDC). M2 and M2a macrophages normally repress T cell expansion, limiting the T cell response. However, when these macrophages were derived from monocytes in Imprime PGG-treated whole blood, they significantly enhanced CD3/CD28-stimulated CD4+ T cell expansion and, importantly, induced production of the potent, anti-tumor cytokine IFN-γ.
Imprime PGG treatment of whole blood also triggered the maturation of MoDC, evident from increased expression of the maturation and co-stimulatory markers that enable efficient antigen presentation. Like macrophages derived from Imprime PGG-treated whole blood, these MoDC were also able to elicit expansion of the CD4+ and CD8+ T cells as well as increased IFN-γ production. Imprime PGG’s ability to enhance M2 and MoDC-mediated T cell expansion was maintained even in the presence of tumor-conditioned media, which normally represses T cell responsiveness.
“These results demonstrate that Imprime PGG treatment drives a coordinated immune response, modulating the function of M2 macrophages and MoDC, enabling the expansion of CD4+ and CD8+ T cells, and driving Th1 polarization,” said Dr. Graff. “These results suggest the potential of combining Imprime PGG treatment with therapies that relieve tumor-mediated T cell immunosuppression.”
Biothera’s research (Abstract #LB-225) 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 modulates the function of monocyte-derived M2 macrophages and dendritic cells to drive T-cell expansion.”
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.