Abstract 2223: A novel protein nanoparticle antigen delivery platform combined with checkpoint inhibition has curative efficacy in the aggressive B16-F10 melanoma model
Authors: Jo Anne Tucker, Medea Neek, Szu-Wen Wang, Edward L. Nelson
Journal: Cancer Research (2020)

Abstract We have developed a novel, non-viral nanoparticle-based vaccine platform that has shown exciting promise for cancer antigen delivery to increase antigen-specific anti-tumor immune responses and significantly prolong survival in the aggressive B16-F10 melanoma model. Our non-viral protein nanoparticle has advantageous properties for antigen delivery and vaccine development. Nanoparticle studies have shown that there is an optimal size range for passive transport in the lymphatic system and uptake by antigen-presenting cells (approximately 20-45 nm); our particle is in this size range. Biodistribution studies of the nanoparticle have shown that they are effectively taken up by almost 50% of DCs within the draining lymph nodes. The structure of the nanoparticle allows for independent functionalization of its internal hollow cavity and external surface, enabling efficient and simultaneous adjuvant and antigen co-delivery. We, as have others, found that vaccine-elicited anti-tumor immune responses are insufficient to cure animals in this model.Immune checkpoint inhibition has provided significant clinical benefit and become an effective alternative treatment to standard chemotherapies in some tumor types. It is believed that immune checkpoint inhibition releases the brake on the existing anti-tumor immune response; however, even in the tumor types where there is clinical benefit, a significant proportion of patients fail to achieve long-term remission. We hypothesized that the combination of our anti-tumor protein nanoparticle vaccine ("E2"; to further prime the immune system to specific tumor-associated antigens) and immune checkpoint blockade will be synergistic and yield improved efficacy, even in the aggressive B16-F10 melanoma tumor model. Immunization with simultaneous delivery of CpG (adjuvant) and gp100 (melanoma MHC-I restricted antigen) within E2 nanoparticles results in significantly increased gp100-specific IFN-γ production by ELISpot, CD8 T cell count in the spleen, tumor-infiltrating CD8 T cell population, and survival time in the B16-F10 murine melanoma model. The combination of the CpG-gp-E2 nanoparticle with anti-PD-1 therapy significantly increased long-term survival; approximately 50% of the mice treated with combination therapy remained tumor-free for up to 60 days (cure) in mice that were inoculated with the poorly immunogenic B16-F10 syngeneic melanoma 24 hours prior to initiating treatment; this is compared with 0% and ≈5% for CpG-gp-E2 and anti-PD-1 treatments alone, respectively. The very limited efficacy of immune checkpoint inhibition in this model is well documented. Thus, this result is more significant. Evidence of a durable anti-tumor response was also observed upon tumor re-challenge. These investigations show that the combination of checkpoint inhibition with antigen delivery using a non-viral protein nanoparticle significantly improves the efficacy over vaccine or immune checkpoint blockade alone.To our knowledge, this is the first report demonstrating the synergistic effects of combination therapy of anti-PD-1 with protein-based nanoparticle vaccines. These data support the exceptional utility of our E2 nanoparticle-based vaccines, especially when combined with immune checkpoint blockade. Citation Format: Jo Anne Tucker, Medea Neek, Szu-Wen Wang, Edward L. Nelson. A novel protein nanoparticle antigen delivery platform combined with checkpoint inhibition has curative efficacy in the aggressive B16-F10 melanoma model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2223.