Syngeneic B16-F1 cells are more efficient than allogeneic Cloudman cells as antigen source in DC-based vaccination in the B16-F1 murine melanoma model. Issue 35 (14th August 2019)

• Record Type: Journal Article
• Authors: Mac Keon, Soledad; Bentivegna, Sofía; Levy, Estrella M.; Marks, Michael S.; Mantegazza, Adriana R.; Wainstok, Rosa; Mordoh, José
• Is Part Of: Vaccine. Volume 37:Issue 35(2019)
• Page Start: 4947
• Page End: 4955
• Publication Date: 2019-08-14
• Subjects: Anti-melanoma vaccination -- Dendritic cells -- Tumor-associated antigens -- Neoepitopes -- Allogeneic cells -- Syngeneic cells; Ab antibody -- ALLO allogeneic -- AnV Annexin V -- ApoNec 48-hour cultured 70Gy irradiated cells (Apoptotic and Necrotic cells) -- CTAs cancer-testis antigens -- DC dendritic cell -- DC-ApoNec dendritic cells loaded with ApoNec cells during 24-hour co-culture. -- MDAs melanocyte differentiation antigens -- MFI mean fluorescence intensity -- MIIC MHC-class II positive tubulovesicular compartments -- PI propidium iodide -- s.c. subcutaneous -- SYN syngeneic -- TAAs tumor-associated antigens; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.07.018
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: A major obstacle to obtaining relevant results in cancer vaccination has been the lack of identification of immunogenic antigens. Dendritic cell (DC)-based cancer vaccines used preventively may afford protection against tumor inoculation, but the effect of antigen choice on anti-tumor protection is not clear. When using irradiated syngeneic tumor cells to load DCs, tumor self-antigens are provided, including tumor-associated antigens (TAAs) and neoantigens generated by tumor mutations. On the other hand, allogeneic tumor cells could only supply shared TAAs. To assess the advantages of each source in protective vaccination, we analyzed in C57BL/6 mice the effect of loading DCs with irradiated syngeneic B16-F1 or allogeneic Cloudman melanoma cells; both cell lines were characterized by whole exome sequencing and RNAseq. Tumor cell components from the two irradiated cell lines were efficiently internalized by DCs, and transported to MHC-class II positive tubulovesicular compartments (MIICs). DCs loaded with allogeneic irradiated Cloudman cells (DC-ApoNecALLO ) induced a partially effective anti-melanoma protection, although Cloudman and B16-F1 cells share the expression of melanocyte differentiation antigens (MDAs), cancer-testis antigens (CTAs) and other TAAs. DCs loaded with syngeneic B16-F1 cells (DC-ApoNecSYN ) established a more potent and long-lasting protection and induced a humoral anti-B16F1 response, thus suggesting that neoepitopes are needed for inducing long-lasting protection.