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A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients

Gene Therapy volume 16, pages 376–382 (2009)Cite this article

Abstract

Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors through enhanced oncolytic activity and HSP-mediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 × 107 to 3.0 × 1012 viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 × 1012 VP and transient grade IV thrombocytopenia at the dose of 3.0 × 1012 VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4+ and CD8+ T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.

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Acknowledgements

This phase I clinical study of H103 was partially supported by the National High Technology Research and Development Program of China (2002AA2Z3340). We gratefully acknowledge Dr Shun-Jiang Yu, Dr Hai-Feng Feng and Dr Rong Zhu for their review of the paper.

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  1. J-L Li and H-L Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Chinese Academy of Medical Sciences, Cancer Hospital, Peking, PR, China

    J-L Li, X-R Zhang, J-P Xu & D-T Chu

  2. Medical Department, Sunway Biotech Co. Ltd, Shanghai, PR, China

    H-L Liu, W-K Hu, M Liang & F Hu

  3. Gene & Immunotherapy Section, Institute of Immunology, Third Military Medical University, PLA, Chongqing, PR, China

    H-L Liu

  4. Department of Molecular and Human Genetics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    S-Y Chen

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  1. J-L Li
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Correspondence to D-T Chu.

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Li, JL., Liu, HL., Zhang, XR. et al. A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients. Gene Ther 16, 376–382 (2009). https://doi.org/10.1038/gt.2008.179

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