Cancerology Laboratory, Fundación Instituto Leloir - IIBBA-CONICET, Buenos Aires, Argentina.
Cancerology Laboratory, Fundación Instituto Leloir - IIBBA-CONICET, Buenos Aires, Argentina.
Vaccine. 2019 Aug 14;37(35):4947-4955. doi: 10.1016/j.vaccine.2019.07.018. Epub 2019 Jul 13.
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-ApoNec) 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-ApoNec) 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.
在癌症疫苗接种中,获得相关结果的主要障碍一直是缺乏免疫原性抗原的鉴定。基于树突状细胞 (DC) 的癌症疫苗可预防性使用,可能提供针对肿瘤接种的保护,但抗原选择对抗肿瘤保护的影响尚不清楚。当使用辐照同基因肿瘤细胞负载 DC 时,会提供肿瘤自身抗原,包括肿瘤相关抗原 (TAA) 和肿瘤突变产生的新抗原。另一方面,同种异体肿瘤细胞只能提供共享的 TAA。为了评估每种来源在保护性疫苗接种中的优势,我们在 C57BL/6 小鼠中分析了用辐照同基因 B16-F1 或同种异体 Cloudman 黑色素瘤细胞负载 DC 的效果;这两种细胞系均通过全外显子组测序和 RNAseq 进行了特征分析。两种辐照细胞系的肿瘤细胞成分被 DC 有效内化,并转运到 MHC 类 II 阳性管状小泡区室 (MIIC)。用同种异体辐照 Cloudman 细胞负载的 DC (DC-ApoNec) 诱导了部分有效的抗黑色素瘤保护作用,尽管 Cloudman 和 B16-F1 细胞共享黑色素细胞分化抗原 (MDA)、癌症睾丸抗原 (CTA) 和其他 TAA 的表达。用同基因 B16-F1 细胞负载的 DC (DC-ApoNec) 建立了更强大和持久的保护作用,并诱导了针对 B16F1 的体液免疫反应,这表明需要新表位来诱导持久的保护作用。