Biohybrid Nanovaccines in Murine Melanoma: Efficacy and Synergistic Combo Therapy with Immune Checkpoint Inhibitor

Immunotherapy relies on the involvement of the patient’s immune system to control the growth of the tumor by, e.g., the administration of immune checkpoint inhibitors, has recently led to increased long-term survival in cancer patients. Amongst the different immunotherapies evaluated in the last years, cancer vaccines are investigated as tools to prime tumor-specific immunity. Biomaterials and, particularly, nano-sized particles, have demonstrated potential as adjuvants in vaccine formulations. The choice of the proper antigenic source is of the uttermost importance for a widespread action against cancer: lately, biomimetic elements derived from the membrane of tumors cells have been evaluated as innovative antigenic sources. Here, we developed a biohybrid cancer nanovaccine and assessed its efficacy in aggressive murine melanoma tumor models in vivo. Porous silicon nanoparticles coated with acetalated dextran formed the core of the formulation that was enriched with the antigenic component through a coating derived from tumor cell membranes [1]. The nanovaccine is cytocompatible and promoted the maturation of murine antigen presenting cells in vitro. Moreover, mice treated twice with the complete nanovaccine formulation showed remissions and control on the tumor progression: the immunological profile of the tumor microenvironment was modified, augmenting the number of mature dendritic cells. We also investigated the effect of a combinatorial therapy with the administration of anti-CTLA4 checkpoint inhibitor together with the biohybrid nanovaccine. The combo therapy results in a synergistic effect, improving the efficacy of both treatments (87.5% of the animals responding, with 2 remissions), reflected also in an increased number of cytotoxic lymphocytes in the tumor microenvironment. This platform thereby shows very promising applications as cancer nanovaccine and promoting a synergistic effect with the standard clinical care treatment for melanoma cancers.

References
[1] Fontana. F (2017), Multistaged Nanovaccines Based on Porous Silicon@Acetalated Dextran@Cancer Cell Membrane for Cancer Immunotherapy, Adv Mater, 29, 1603239.