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Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

Cancer Gene Therapy volume 16, pages 598–608 (2009)Cite this article

Abstract

DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine's potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 μg naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-γ (IFN-γ) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-γ responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals.

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Acknowledgements

This study was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico).

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Author notes

  1. K Abdallah

    Present address: 7Current address: Bristol Myers Squibb Company, Route 206 & Provinceline Road, Office number - J2713, Princeton NJ, 08543-4000, USA,

Authors and Affiliations

  1. Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of Sao Paulo, Sao Paulo, SP, Brazil

    G D Victora, A Socorro-Silva, E C Volsi, J Kalil & V Coelho

  2. Institute for Investigation in Immunology—Millennium Institute, University of Sao Paulo, Sao Paulo, SP, Brazil

    G D Victora, A Socorro-Silva, E C Volsi, K Abdallah, F D Lima, J Kalil & V Coelho

  3. Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Sao Paulo, Brazil

    G D Victora

  4. Division of Clinical Immunology and Allergy, University of Sao Paulo, Sao Paulo, SP, Brazil

    A Socorro-Silva, E C Volsi, K Abdallah, F D Lima, J Kalil & V Coelho

  5. Division of Head and Neck Surgery, Department of Surgery, School of Medicine, University of Sao Paulo, Sao Paulo, SP, Brazil

    R B Smith, R A Moyses & P Michaluart

  6. Centre for Tuberculosis Research, REDE TB Millennium Institute, School of Medicine of Ribeirão Preto, University of Sao Paulo, Ribeirão Preto, SP, Brazil

    C R Zárate-Bladés & C L Silva

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  1. G D Victora
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Correspondence to V Coelho.

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Victora, G., Socorro-Silva, A., Volsi, E. et al. Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients. Cancer Gene Ther 16, 598–608 (2009). https://doi.org/10.1038/cgt.2009.9

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  • DOI: https://doi.org/10.1038/cgt.2009.9

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