Abstract
BackgroundFuture cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies:...
Highlights
Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms
We found that the treatment combination provided enhanced therapeutic control of tumors, which could be attributed to an enrichment in the expansion of vaccine-induced antigen specific CD8+ T cells
We have demonstrated that the DPX/metronomic cyclophosphamide (mCPA) combination is effective in inducing antigen-specific CD8+ T cells that could effectively control small tumors in our preclinical model, the efficacy was limited in the treatment of more advanced tumors [6]
Summary
Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. The DPX formulation utilizes lipids to effectively combine multiple peptide or protein antigens and adjuvants into an oil phase, resulting in a formulation that uniquely provides a long lasting and immunogenic depot in vivo [7]. We found that the treatment combination provided enhanced therapeutic control of tumors, which could be attributed to an enrichment in the expansion of vaccine-induced antigen specific CD8+ T cells. These results were translated to a Phase 1/1b clinical trial evaluating DPX-Survivac, a DPX vaccine containing multiple peptide antigens derived from the tumor associated protein survivin (DPX-Survivac), and mCPA in advanced ovarian cancer patients [5]. Due of the multiple effects of cyclophosphamide on the immune system, combinations with other forms of immune therapy must be individually assessed
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