Dendritic cells loaded with allogeneic melanoma and non-melanoma tumor cells provide protection against melanoma based on shares tumor-associated antigens.

MORDOH, JOSÉ; MARKS, MICHAEL S; MAC KEON, SOLEDAD; WAINSTOK, ROSA; LEVY, ESTRELLA MARIEL; MANTEGAZZA, ADRIANA; BENTIVEGNA, SOFÍA

Simposio; 15th International Symposium on Dendritic Cells; 2018

Dendritic cell (DC)-based cancer immunotherapy can be achieved by loading DCs with syngeneic or allogeneic cells, but the consequences brought upon antigen processing and anti-tumor protection are not clear. When using syngeneic tumor cells, tumor self-antigens are provided, including tumor-associated antigens (TAAs) and neoantigens generated through mutations during tumor progression. On the other hand, allogeneic tumor cells can supply shared TAAs and allo-MHC-I. To assess the advantages of each system, we have analysed in a murine model the effect on anti-melanoma protection of loading bone-marrow derived DCs with irradiated syngeneic B16-F1, allogeneic Cloudman melanoma, or allogenic 4T1 breast cancer cells, which were characterized by whole exome sequencing and RNAseq. We observed that irradiated tumor cell components were efficiently internalized by DCs, transported to Lamp1+ phagolysosomes and within MHC-class II positive tubulovesicular compartments. In vivo, syngeneic B16-F1 and allogeneic Cloudman DC-ApoNec preventive vaccination induced an effective anti-melanoma protection, 100% and 60% of the animals remaining tumor-free, respectively. Short-term and long-term protection were significantly increased by syngeneic compared to allogeneic DC-ApoNec vaccination (p