CXCL10-armed oncolytic adenovirus promotes tumor-infiltrating T-cell chemotaxis to enhance anti-PD-1 therapy

Oncoimmunology. 2022 Aug 31;11(1):2118210. doi: 10.1080/2162402X.2022.2118210. eCollection 2022.

Abstract

Resistance remains an obstacle to anti-programmed cell death protein 1 (PD-1) therapy in human cancer. One critical resistance mechanism is the lack of T cell chemotaxis in the tumor microenvironment (TME). CXCL10-CXCR3 signaling is required for T cell tumor infiltration and tumor immunotherapy. Oncolytic viruses (OVs), including oncolytic adenoviruses (AdVs), induce effective T cell immunity and tumor infiltration. Thus, arming OV with CXCL10 would be an attractive strategy to overcome resistance to anti-PD1 therapy. Here, we successfully constructed a novel recombinant oncolytic adenovirus encoding murine CXCL10, named Adv-CXCL10. Through intratumoural injection, the continuous expression of the functional chemokine CXCL10 in the TME is realized to recruit more CXCR3+ T cells into the TME to kill tumor cells, and the recombinant adenovirus shows great power to 'fire up' the TME and enhance the antitumour efficiency of PD-1 antibodies.

Keywords: CXCL10; CXCR3; Oncolytic virus; anti-PD-1; colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae Infections*
  • Animals
  • Chemokine CXCL10 / genetics
  • Chemotaxis
  • Humans
  • Mice
  • Neoplasms* / therapy
  • Oncolytic Viruses* / genetics
  • Rhabdomyosarcoma, Alveolar*
  • Tumor Microenvironment

Substances

  • CXCL10 protein, human
  • Chemokine CXCL10

Grants and funding

This work was supported by the National Natural Science Foundation of China (Nos. 81871944, 82072675, 81874317); Jiangsu 333 Project (BRA2016517); Jiangsu Province Key Medical Talents (ZDRCA 2016026) and the Fundamental Research Funds for the Central Universities (020814380161)