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Peer-reviewedCC BYMolecular Therapy: Oncology

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

  • Rong Zhang1
  • Tingting Wang1
  • Yu Wang2
  • Chenggang Hong1
  • Yun Qin1
  • Kangchen Ye1
  • Hu Zhao2
  • Fang Hu1
  • Jinlu Cai3
  • Jin Fu4
4 affiliations
  1. 1Hangzhou Converd Co. Ltd., Hangzhou, China
  2. 2Department of General Surgery, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
  3. 3Hangzhou Converd Co. Ltd., Hangzhou, China; Corresponding author: Jinlu Cai, Hangzhou Converd Co. Ltd., Hangzhou, China.
  4. 4Hangzhou Converd Co. Ltd., Hangzhou, China; Corresponding author: Jin Fu, Hangzhou Converd Co. Ltd., Hangzhou, China.
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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.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026interleukin21,
  title = {{Interleukin-21 expressing oncolytic vaccinia virus elicits systemic anti-tumor immune response and synergizes with immunotherapies}},
  author = {Rong Zhang and Tingting Wang and Yu Wang and Chenggang Hong and Yun Qin and Kangchen Ye and Hu Zhao and Fang Hu and Jinlu Cai and Jin Fu},
  journal = {Molecular Therapy: Oncology},
  year = {2026},
  month = sep,
  doi = {10.1016/j.omton.2026.201348},
  url = {https://doi.org/10.1016/j.omton.2026.201348},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Interleukin-21 expressing oncolytic vaccinia virus elicits systemic anti-tumor immune response and synergizes with immunotherapies
AU  - Rong Zhang
AU  - Tingting Wang
AU  - Yu Wang
AU  - Chenggang Hong
AU  - Yun Qin
AU  - Kangchen Ye
AU  - Hu Zhao
AU  - Fang Hu
AU  - Jinlu Cai
AU  - Jin Fu
PY  - 2026
DA  - 2026/09/18
JO  - Molecular Therapy: Oncology
DO  - 10.1016/j.omton.2026.201348
UR  - https://doi.org/10.1016/j.omton.2026.201348
AB  - 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.
SN  - 2950-3299
ER  -