Hyaluronic acid-antigens conjugates trigger potent immune response in both prophylactic and therapeutic immunization in a melanoma model

Immunotherapy of advanced melanoma has encountered significant hurdles in terms of clinical efficacy. Here, we designed a clinically translatable hyaluronic acid (HA)-based vaccine delivering a combination of major histocompatibility complex (MHC) class I- and class II-restricted melanoma antigens (TRP2 and Gp100, respectively) conjugated to HA. HA-nanovaccine (HA-TRP2-Gp100 conjugate) exhibited tropism in the lymph nodes and promoted stimulation of the immune response (2.3-fold higher than the HA+TRP2+Gp100). HA-nanovaccine significantly delayed the growth of B16F10 melanoma and extended survival in both the prophylactic and therapeutic settings (median survival of 22 and 27, respectively, vs 17 days of the untreated group). Moreover, mice prophylactically treated with the HA-nanovaccine displayed significantly higher CD8+ and CD4+ T-cell/Treg ratios in both the spleen and tumor at day 16, suggesting that the HA-nanovaccine overcame the immunosuppressive tumor microenvironment. Superior infiltration of active CD4+ and CD8+ T cells was observed at the endpoint. This study supports the conclusion that HA potentiates the effect of a combination of MHC I and MHC II antigens via a potent immune response against melanoma. Graphical Abstract