Immunovaccine Inc. recently presented new preclinical data at the American Association for Cancer Research Annual Meeting 2016 revealing that a combination immunotherapy using a DepoVax-based vaccine could enhance the anti-tumoral effects of PD-1 blockade in advanced HPV-expressing tumors.
DepoVax is a patented vaccine delivery formulation that provides controlled and prolonged exposure of antigens plus adjuvant to the immune system. The result is a strong, specific, and sustained immune response with the capability for single-dose effectiveness.
Researchers found that the combination of a DepoVax-based vaccine with the chemotherapy metronomic cyclophosphamide (mCPA) augmented PD-1 and PD-L1 proteins in tumor cells’ surface, making them progressively more 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,” Immunovaccine CEO Frederic Ors said in a press release.
“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.”
In the study titled “Multimodal therapy with a potent vaccine, metronomic cyclophosphamide and anti-PD-1 enhances immunotherapy of advanced tumors by increasing activation and clonal expansion of tumor infiltrating T cells,” the team assessed the DepoVax-based vaccine combined with mCPA and a PD-1 blockade (either anti-PD-1 or anti-PD-L1) in a preclinical tumor model to test its anti-cancer effects.
Treatment combination was able to control tumor growth, making this the first study to show how combining DepoVax-based vaccine, mCPA, and a PD-1 blockade increases the activation and clonal expansion of tumor-infiltrating T cells.
Specifically, treatment with DepoVax and mCPA selectively enriched antigen-specific CD8+ T-cells, increasing immune responses. Furthermore, anti-PD-1 therapy enhanced the efficacy of the vaccine immunotherapy as it promoted the activity and expansion of antigen-specific T-cells within the tumor microenvironment.
These results provide a rationale for clinical testing of checkpoint blockade therapy in combination with the highly immunogenic combination of mCPA and DepoVax. Moreover, assessment of T-cell clonality within the tumor may be an important biomarker for immunomodulatory treatments.
“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 Marianne Stanford, Ph.D., Immunovaccine 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,” she said.
The DepoVax platform possesses impressive flexibility, allowing it to work with an extensive range of target antigens for many therapeutic purposes. The platform is also commercially scalable, with potential for years of stability and ease of use in the clinic.
To date, DepoVax has served as the basis for Immunovaccine’s two clinical-stage cancer immunotherapies, as well as a number of partnered vaccine programs spanning infectious diseases, bio-terrorism, addiction medicine, and animal health. Collaborators include many leaders in their respective areas of focus, including the National Institutes of Health and Zoetis (formerly Pfizer Animal Health).