Work

Interleukin-21 expressing oncolytic vaccinia virus elicits systemic anti-tumor immune response and synergizes with immunotherapies

Year: 2026

Type: article

Abstract: A successful oncolytic virus is critical to therapeutic success, requiring the identification of an effective viral platform and immunomodulatory molecules that potently promote host immune responses and reprogram the tumor microenvironment (TME). In the present study, we developed V01, an oncolytic virus derived from the Western Reserve (WR) strain of vaccinia virus, featuring double deletions of the vaccinia growth factor (VGF) and thymidine kinase (TK) genes, along with the expression of interleukin-21 (IL-21). Locally administered intratumoral (i.t.) V01 elicited systemic anti-tumor effects against both the primary injected tumor and distant non-injected tumors in immunocompetent tumor-bearing mice. Abscopal effects of V01 were observed in homologous tumors but not in heterologous tumors. Combination treatment of V01 with immunotherapeutic agents-PD-1 antibody or natural killer (NK) cell therapy-exhibited synergistic tumor regression. Together, these results suggest that V01 holds significant promise as a novel immunotherapeutic or immunoadjuvant for solid tumor treatment, warranting further clinical investigation.

Source: Molecular Therapy Oncology

DOI: 10.1016/j.omton.2026.201348