HALIFAX, Nova Scotia—Immunovaccine Inc., a clinical stage vaccine and immunotherapy company, presented new preclinical data at the annual meeting of the American Association for Cancer Research recently in which the investigators’ findings showed that a combination immunotherapy using a DepoVax-based vaccine could enhance the antitumor effects of a PD-1 blockade, controlling growth in advanced HPV-expressing tumors in animal models.
Investigators concluded that combining a DepoVax-based vaccine with the chemotherapy metronomic cyclophosphamide (mCPA) increased PD-1 and PD-L1 in tumors, which in turn made them increasingly vulnerable to the monoclonal antibody treatment targeting these checkpoint inhibitors.
“Checkpoint inhibitors have shown tremendous promise in treating certain types of cancers, and our industry is now racing to discover and develop combination therapies to make these treatments effective across a broader range of patients,” said Frederic Ors, Immunovaccine’s CEO. “This study shows how our DepoVax-based vaccines can become an integral part of these therapies, as they have the potential to increase the susceptibility of tumors to PD-1 blockades, even in tumors that typically do not respond to checkpoint inhibitor therapies. We are currently evaluating opportunities to pursue partnerships, leveraging our DepoVax-based vaccines to increase the efficacy of the checkpoint inhibitors in development or currently on the market.”
Presented as a poster at AACR 2016, the study evaluated the anticancer effects of a DepoVax-based vaccine combined with mCPA and a PD-1 blockade (either anti-PD-1 or anti-PD-L1) in a preclinical tumor model. The tumor model used in the study has a relatively low expression of PD-1 and PD-L1. The study treatment combination resulted in growth control of established tumors, even those that were not successfully treated with antibody monotherapy alone.
In addition to the efficacy findings, the study is reportedly the first to show how the combination of a DepoVax-based vaccine, mCPA and a PD-1 blockade can work synergistically to increase activation and clonal expansion of tumor-infiltrating T cells.
Two key findings were: (1) that treatment with a DepoVax-based vaccine and mCPA caused selective enrichment of antigen-specific CD8+ T cells, which increased immune responses, and (2) that anti-PD-1 therapy can enhance the efficacy of vaccine immunotherapy by promoting the activity and expansion of antigen-specific T cells within the tumor microenvironment.
Investigators concluded that inoculation with the DepoVax-based vaccine generated an influx of T cells into tumors, essentially priming the tumor for additional anticancer activity when combined with PD-1 blockade.
“The findings support our contention that stimulating high-quality T cell responses to the tumor is a key to inducing stronger clinical responses, particularly for those cancers that do not respond to PD-1 treatment alone,” said Dr. Marianne Stanford, Immunovaccine’s director of research. “While we’ve always reasoned that our DepoVax-based vaccines would work synergistically with blockade therapies, this study actually showed us how and why this happens. These findings provide us with a roadmap to inform our future clinical strategy for combining our DepoVax-based vaccines, including our DPX-Survivac vaccine candidate, with checkpoint therapies.”
DepoVax is a patented formulation that provides controlled and prolonged exposure of antigens plus adjuvant to the immune system, resulting in “a strong, specific and sustained immune response with the potential for single-dose effectiveness,” according to Immunovaccine. The DepoVax platform is flexible and can be used with a broad range of target antigens for preventative or therapeutic applications, the company says.
Immunovaccine has advanced two T cell activation therapies for cancer through Phase 1 human clinical trials and is currently conducting a Phase 2 study with its lead cancer vaccine therapy, DPX-Survivac, in recurrent lymphoma. DPX-Survivac is expected to enter additional Phase 2 clinical studies in ovarian cancer and glioblastoma. In collaboration with commercial and academic partners, Immunovaccine is also expanding the application of DepoVax as an adjuvanting platform for vaccines targeted against infectious diseases. Immunovaccine’s goal in infectious diseases is to out-license its DepoVax platform to partners to generate earlier revenues.