Description

Syngneic vs allogeneic cells as antigen source for anti-melanoma vaccination

Soledad Mac Keon^1*, Estrella Levy², Rosa Wainstok^3,4, José Mordoh¹

¹Fund. Inst. Leloir-IIBBA, Bs As; ²CIO-FUCA, Bs As; ³IQUIBICEN-CONICET-UBA, Bs As; ⁴Dep.Quím. Biol., FCEN, UBA, Bs As

*Corresponding Author

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.