Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine pancreatic cancer.

ABSTRACT: Tumor neoantigens arising from somatic mutations in the cancer genome are less likely to be subject to central immune tolerance and are therefore attractive targets for vaccine immunotherapy. We utilized whole-exome sequencing, RNA sequencing (RNASeq), and an in silico immunogenicity prediction algorithm, NetMHC, to generate a neoantigen-targeted vaccine, PancVAX, which was administered together with the STING adjuvant ADU-V16 to mice bearing pancreatic adenocarcinoma (Panc02) cells. PancVAX activated a neoepitope-specific T cell repertoire within the tumor and caused transient tumor regression. When given in combination with two checkpoint modulators, namely anti-PD-1 and agonist OX40 antibodies, PancVAX resulted in enhanced and more durable tumor regression and a survival benefit. The ad

SUBMITTER: Kinkead HL 

PROVIDER: S-EPMC6237485 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature