A New Melanoma Vaccine Based on Conditioned Tumor Cell Lysates potentiates anti PD1 treatment Inhibiting Tumor Growth
Alejandra Gleisner1,2, Ignacio Avalos1,2, Fabián Tempio1,2, Mariela Navarrete1,2, Andrés Tittarelli1,2, Mercedes López1,2, Fermín González1, Cristian Pereda1,2, Flavio Salazar-Onfray1,2
1Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; 2Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile
Clinical strategies using immune-checkpoint blockers, such as 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 may improve responses rate. In this context, cancer vaccines become again a complementary alternative as cancer treatment. 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 conditioned melanoma allogeneic tumor lysates (TRIMEL) combined with a specific adjuvant already used in the context of a DC vaccine, without adverse effects. The vaccine is intended to directly activate the immune response against tumor in vivo, inhibiting its growth. TRIMELVax was evaluated, in terms of safety and efficacy at pre-clinical level, in C57Bl/6 murine model of melanoma (B16). In short, immunocompetent mice was vaccinated with three doses of TRIMELVax, and then challenged with B16 melanoma cells. Alternative, immunization was also tested therapeutically in tumor bearing mice. Our results showed that only TRIMELVax was capable to reduce drastically the occurrence of tumor, inhibiting tumor growth in immunized mice. In contrast the separated use of tumor lysate, or adjuvant did not impact tumor growth. This response was associated to CD8+ T cells mediated immune response and antibody production. Anti-PD1 therapy were strongly potentiated by the 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.