A nanovaccine induces durable and functional MUC4-targeted T cell responses against pancreatic cancer

Vaccination against cancer for prophylaxis or treatment is becoming a viable approach owing to new developments in the identification of novel biomarkers and advances in our understanding of cancer immunology. Furthermore, nanotechnology has resulted in multifunctional delivery platforms with versatile chemistries and tunable release properties. However, despite this impressive progress, immunotherapy with the goal of inducing antigen-specific T cell immunity against pancreatic cancer (PC) remains challenging. Herein, we report the characterization of the long-lived humoral and cellular immunity towards a promising PC antigen (MUC4) after immunization with either polyanhydride or poly(lactic-co-glycolic acid) particle-based adjuvanted vaccines. T cell response dynamics from both draining lymph nodes and spleens after three immunizations were monitored for up to 180 days. Through a systematic characterization of antigen-specific immunity at various timepoints and organs, a dynamic picture of T cell immunity emerges that suggests differentiation and migration of T cells, Th1 cell polarization, polyfunctional CD4⁺ and CD8⁺ T cell cytokine expression, and cytotoxicity towards PC cells. Overall, the results showed that MUC4-nanovaccines induced durable MUC4-specific T cell responses both locally and systemically, which portends well for sustained anti-tumor immunity. STATEMENT OF SIGNIFICANCE: Immunotherapy with the goal of inducing antigen-specific T cell immunity against pancreatic cancer (PC) remains challenging. We characterized long-lived humoral and cellular immunity towards a promising PC antigen (MUC4) after immunization with either polyanhydride or poly(lactic-co-glycolic acid) particle-based adjuvanted vaccines. A systematic characterization of antigen-specific immunity at various timepoints and organs uncovered a dynamic picture of T cell immunity that demonstrated differentiation and migration of T cells, Th1 cell polarization, polyfunctional CD4⁺ and CD8⁺ T cell cytokine expression, and cytotoxicity towards PC cells. The findings indicated that MUC4 nanovaccines induced durable MUC4-specific T cell responses both locally and systemically, which portends well for sustained anti-tumor immunity.