Syngneic vs allogeneic cells as antigen source for anti-melanoma vaccination
Soledad Mac Keon1*, Estrella Levy2, Rosa Wainstok3,4, José Mordoh1
1Fund. Inst. Leloir-IIBBA, Bs As; 2CIO-FUCA, Bs As; 3IQUIBICEN-CONICET-UBA, Bs As; 4Dep.Quím. Biol., FCEN, UBA, Bs As
One of the major obstacles to obtaining relevant results in cancer immunotherapy has been the unclear definition of relevant target antigens. It is still uncertain whether an autologous (containing neo-epitopes) or allogeneic source of antigen (containing tumor-associated antigens) is better at eliciting potent anti-tumoral protection. We have previously developed an experimental anti-melanoma vaccine (DC-ApoNec) consisting of dendritic cells (DC) loaded with syngeneic apoptotic and necrotic murine melanoma cells (ApoNec), which provides long-term anti-melanoma protection. Using this vaccine, we have compared the use of syngeneic or allogeneic ApoNec cells as source of antigen, and its effect on DCs and on anti-tumoral protection. We have determined by qPCR the comparable expression of immunogenic melanocyte differentiation antigens by syngeneic B16-F1 and allogeneic Cloudman murine cell lines. We have observed a low MHC-I expression by both cell lines. When loading DCs with ApoNec cells obtained by irradiation of these cell lines we observed that 60.3±21.1 % and 71.0±19.4% of CD11c+ cells incorporated B16-F1 ApoNec or Cloudman ApoNec cells respectively, but that Cloudman ApoNec cells were more efficient at inducing MHC-II upregulation by CD11c+ cells (p<0.05). In vivo, syngeneic and allogeneic DC-ApoNec 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<0.05). Additionally, syngeneic vaccination induced a humoral anti-B16-F1 response while allogeneic vaccination failed to do so. Thus, although melanoma-associated antigens from allogeneic cells provide an efficient anti-melanoma protection, neo-epitopes could be necessary to generate a more potent and long-lasting protection.
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