免疫系统
细胞毒性T细胞
接种疫苗
癌症
CD8型
免疫
肿瘤抗原
CTL公司*
免疫学
抗体
肽疫苗
生物
埃利斯波特
作者
Victoria M. Kim,Xingyi Pan,Kevin C. Soares,Nilofer S. Azad,Nita Ahuja,Christopher Gamper,Alex B. Blair,Stephen Muth,Ding Ding,Brian H. Ladle,Lei Zheng
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2020-05-07
卷期号:5 (9)
被引量:9
标识
DOI:10.1172/jci.insight.136368
摘要
Metastatic colorectal cancer (CRC) is poorly immunogenic, with limited neoantigens that can be targeted by cancer vaccine. Previous approaches to upregulate neoantigen have had limited success. In this study, we investigated the role of a DNA methyltransferase inhibitor (DNMTi), 5-aza-2'-deoxycytidine (DAC), in inducing cancer testis antigen (CTA) expression and evaluated the antitumor efficacy of a combinatorial approach with an epigenetically regulated cancer vaccine EpiGVAX and DAC. A murine model of metastatic CRC treated with combination therapy with an irradiated whole-cell CRC vaccine (GVAX) and DAC was used to assess the antitumor efficacy. DAC significantly induced expression of CTAs in CRC, including a new CTA Tra-P1A with a known neoepitope, P1A. Epigenetically modified EpiGVAX with DAC improved survival outcomes of GVAX. Using the epigenetically regulated antigen Tra-P1A as an example, our study suggests that the improved efficacy of EpiGVAX with DAC may due in part to the enhanced antigen-specific antitumor immune responses. This study shows that epigenetic therapy with DNMTi can not only induce new CTA expression but may also sensitize tumor cells for immunotherapy. Neoantigen-based EpiGVAX combined with DAC can improve the antitumor efficacy of GVAX by inducing antigen-specific antitumor T cell responses to epigenetically regulated proteins.
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