IL-23-engineered oncolytic vaccinia virus enhances pancreatic cancer control through inflammasome-driven Th17-skewed CD4⁺ T-cell responses.

ABSTRACT:

Background

Oncolytic viruses represent a promising immunotherapeutic strategy for converting pancreatic and other immunologically cold tumors. While their ability to stimulate innate immune signaling and promote antitumor immunity is established, mechanisms enabling durable adaptive responses remain poorly defined.

Methods

We used CRISPR-Cas9-based homologous recombination to generate a thymidine kinase (TK) and B2R double-deleted backbone virus, VV∆TK∆B2R (VV-DD). On this backbone, we engineered VV∆TKmp40∆B2Rmp19 (VV-DDIL23), which expresses the p40 and p19 subunits of interleukin-23 (IL-23) separately to mimic natural heterodimer assembly. Its antitumor efficacy was evaluated in immunosuppressive pancreatic ductal adenocarcinoma models and compared with a single-chain IL-2

SUBMITTER: Guo Y 

PROVIDER: S-EPMC13630030 | biostudies-literature | 2026 Sep

REPOSITORIES: biostudies-literature