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Intratumoral delivery of a Tim-3 antibody-encoding oncolytic adenovirus engages an effective antitumor immune response in liver cancer

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Abstract

Background and Purpose

The use of oncolytic viruses as a gene therapy vector is an area of active biomedical research, particularly in the context of cancer treatment. However, the actual therapeutic success of this approach to tumor elimination remains limited. As such, the present study was developed with the goal of simultaneously enhancing the antitumor efficacy of oncolytic viruses and the local immune response by combining the Ad-GD55 oncolytic adenovirus and an antibody specific for the TIM-3 immune checkpoint molecule (α-TIM-3).

Approach and Key Results

The results of Virus and cell-mediated cytotoxicity assay, qPCR, and Western immunoblotting showed that Ad-GD55–α-Tim-3 oncolytic adenovirus is capable of inducing α-TIM-3 expression within hepatoma cells upon infection, and Ad-GD55–α-TIM-3 exhibited inhibitory efficacy superior to that of Ad-GD55 when used to treat these tumor cells together with the induction of enhanced intracellular immunity. In vivo experiments revealed that Ad-GD55–α-TIM-3 administration was sufficient to inhibit tumor growth and engage in a more robust local immune response within the simulated tumor immune microenvironment.

Conclusion and Implications

These results highlighted the promising therapeutic effects of Ad-GD55–α-TIM-3 oncolytic adenovirus against HCC in vitro and in vivo. As such, this Ad-GD55–α-TIM-3 oncolytic adenovirus may represent a viable approach to the treatment of hepatocellular carcinoma.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

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Funding

The research leading to these results received funding from the Applied Research and Cultivation Program of Jiangxi Province, No. 20212BAG70043; the Public Welfare Technology Project of Zhejiang Province, No. LGF21H160033; Zhejiang Medical Technology Plan Project, No. 2021KY047; Hangzhou Science and Technology Bureau, No. 20201203B44; Hangzhou Medical Health Science and Technology Project, No. B20220173; the National Natural Science Foundation of China, No. 81803069 and the Grant for 521 talent project of ZSTU.

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Authors and Affiliations

  1. College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Li Qiang, Zhang Huili, Zhang Leilei, Huang Biao & Wang Yigang

  2. Surgical Department of Duchang County Second People’s Hospital, Jiujiang, 332600, China

    Li Qiang & Wang Yiqiang

  3. Oncology Department, Zhejiang Xiaoshan HospitaI, Hangzhou, China

    Wang Xiaoyan & Wang Hui

  4. Department of Pathology, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, China

    Huang Fang

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  1. Li Qiang
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  2. Zhang Huili
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  3. Zhang Leilei
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  4. Wang Xiaoyan
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  5. Wang Hui
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  6. Huang Biao
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Contributions

The writing of the article was mainly completed by LQ and WYG., the experimental part was mainly completed by LQ., and the technical support was provided by ZLL, ZHL, WF, WH, WYQ and WXY. All authors reviewed the manuscript.

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Correspondence to Wang Yigang, Huang Fang or Wang Yiqiang.

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Qiang, L., Huili, Z., Leilei, Z. et al. Intratumoral delivery of a Tim-3 antibody-encoding oncolytic adenovirus engages an effective antitumor immune response in liver cancer. J Cancer Res Clin Oncol 149, 18201–18213 (2023). https://doi.org/10.1007/s00432-023-05501-8

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