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Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck

Cancer Gene Therapy volume 15, pages 676–684 (2008)Cite this article

Abstract

Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 μg of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 μg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 μg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.

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Acknowledgements

We would like to thank Roger Chammas for his useful advice during the planning of the trial, Dr José Maciel Rodrigues Jr and Dr Karla Lima for their help in vaccine production. This work was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and FINEP (Financiadora de Estudos e Projetos).

Author information

Author notes

  1. K A Abdallah

    Present address: 11Current address: Bristol Myers Squibb, Plainsboro, NJ 0853, USA,

Authors and Affiliations

  1. HSP65 Clinical Trial Group, University of São Paulo, São Paulo, Brazil

    P Michaluart, K A Abdallah, F D Lima, R Smith, R A Moysés, V Coelho, G D Victora, A Socorro-Silva, E C Volsi, C R Zárate-Bladés, A R Ferraz, A K Barreto, M C Chammas, R Gomes, E Gebrim, L Arakawa-Sugueno, K P Fernandes, P A Lotufo, M R Cardoso, J Kalil & C L Silva

  2. Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil

    P Michaluart, R Smith, R A Moysés, A R Ferraz, L Arakawa-Sugueno & K P Fernandes

  3. Department of Immunology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil

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

  4. Institute for Investigation in Immunology—Millennium Institute, University of São Paulo, São Paulo, Brazil

    P Michaluart, K A Abdallah, V Coelho & J Kalil

  5. Department of Biochemistry and Immunology, The Centre for Tuberculosis Research, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    C R Zárate-Bladés & C L Silva

  6. Department of Radiology, University of São Paulo Medical School, São Paulo, Brazil

    M C Chammas, R Gomes & E Gebrim

  7. Department of Medicine, University of São Paulo Medical School, São Paulo, Brazil

    P A Lotufo

  8. Department of Epidemiology, Faculty of Public Health, University of São Paulo, São Paulo, Brazil

    M R Cardoso

  9. Millennium Institute for Tuberculosis Research, University of São Paulo, São Paulo, Brazil

    C L Silva

  10. Farmacore Biotechnology Ltd., Ribeirão Preto, São Paulo, Brazil

    C L Silva

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  1. P Michaluart
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Corresponding author

Correspondence to C L Silva.

Additional information

Author contributions

Conception and design: Celio L Silva, Pedro Michaluart, Kald Abdallah, Verônica Coelho.

Administrative support: Celio L Silva and Pedro Michaluart.

Provision of study materials or patients: Celio L Silva, Pedro Michaluart, Kald Abdallah, Raquel A Moysés, Fanny D Lima, Rodney B Smith and Maria Cristina Chammas.

Collection and assembly of data: Pedro Michaluart, Kald Abdallah, Fanny D Lima, Rodney B Smith, Raquel A Moysés, Verônica Coelho, Gabriel D Victora, Jorge Kalil, Alberto R Ferraz, Ana K Barreto, Maria Cristina Chammas, Regina LE Gomes, Eloisa Gebrim, Lica Arakawa-Sugueno, Kariane P Fernandes, Paulo A Lotufo and Maria Regina Cardoso.

Data analysis and interpretation: Pedro Michaluart, Kald Abdallah, Fanny D Lima, Rodney B Smith, Raquel A Moysés, Verônica Coelho, Gabriel D Victora, Adalberto Socorro-Silva, Evelyn C Volsi, Jorge Kalil, Carlos R Zárate-Bladés, Alberto R Ferraz, Ana K Barreto, Regina LE Gomes, Eloisa Gebrim, Lica Arakawa-Sugueno, Kariane P Fernandes, Paulo A Lotufo, Maria Regina Cardoso and Celio L Silva.

Manuscript writing: Celio L Silva, Pedro Michaluart, Verônica Coelho, Carlos R Zárate-Bladés, Gabriel D Victora, Fanny D Lima, Rodney B Smith and Maria Regina Cardoso.

Finnal approval of manuscript: Pedro Michaluart, Kald Abdallah, Fanny D Lima, Rodney B Smith, Raquel A Moysés, Verônica Coelho, Gabriel D Victora, Adalberto Socorro-Silva, Evelyn C Volsi, Jorge Kalil, Carlos R Zárate-Bladés, Alberto R Ferraz, Ana K Barreto, Maria Cristina Chammas, Regina LE Gomes, Eloisa Gebrim, Lica Arakawa-Sugueno, Kariane P Fernandes, Paulo A Lotufo, Maria Regina Cardoso and Celio L Silva.

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Michaluart, P., Abdallah, K., Lima, F. et al. Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck. Cancer Gene Ther 15, 676–684 (2008). https://doi.org/10.1038/cgt.2008.35

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  • DOI: https://doi.org/10.1038/cgt.2008.35

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