Clinical strategies using immune-checkpoint blockers, such as anti-CTLA4, (Ipilimumab) or anti-PD1 antibodies (Nivolumab), have recently demonstrated durable survival benefits in patients with melanoma and other tumors. Nevertheless, an important percentage of treated patients remain refractory, suggesting that combination with other kind of active immunization is required for increasing responses rate. In this context, cancer vaccines become again a complementary alternative. The optimal delivery of antigens (Ags) and the use of adequate adjuvants are crucial for vaccine success. Here, a prototype of a generic therapeutic vaccine for the treatment of malignant melanoma named TRIMELVaxTM was tested in an experimental model. This vaccine is based on heat-shock conditioned melanoma allogeneic tumor lysates combined with specific adjuvants. The vaccine is intended to activate immune responses against tumor in vivo, inhibiting its growth. TRIMELVax was evaluated, in terms of safety and efficacy in C57Bl/6 murine model. In short, immunocompetent mice was vaccinated with three doses of TRIMELVax, and then challenged with B16 murine melanoma cells. Alternatively, immunization was tested therapeutically in tumor bearing mice. Our results showed that only TRIMELVax was capable to reduce the occurrence of tumor. In contrast the use of non-conditioned tumor lysate, or adjuvant alone did not impact tumor growth. Observed response was associated with CD8+ T cells intratumoral accumulation and antibody production in sera. Moreover, anti-PD1 therapy was strongly potentiated by combination with TRIMELVax in immunocompetent mice, which encourage testing of the combined treatment in future clinical trials. Financed by grants FONDECYT 1171213, FONDEF ID16I10148 and MIII P09/016-F.
Flavio Salazar-Onfray– Full Profesor, PhD, Universidad de CHILE