Immune response to vaccination with DNA-Hsp65 in a phase I clinical trial with head and neck cancer patients
| Autor: | E. C. Volsi, F. D. Lima, A. Socorro-Silva, Gabriel D. Victora, Verônica Coelho, Carlos R. Zárate-Bladés, K. A. Abdallah, Raquel Ajub Moyses, Jorge Kalil, Célio Lopes Silva, Rodney B. Smith, Pedro Michaluart |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Cancer Research Enzyme-Linked Immunosorbent Assay medicine.disease_cause Peripheral blood mononuclear cell Cancer Vaccines Drug Administration Schedule Autoimmunity Immune system medicine Vaccines DNA Humans Molecular Biology Mycobacterium leprae Heat-Shock Proteins Aged Immunity Cellular biology business.industry Head and neck cancer Middle Aged medicine.disease biology.organism_classification Vaccination Immunization Head and Neck Neoplasms Immunology Antibody Formation biology.protein Carcinoma Squamous Cell Molecular Medicine Female Immunotherapy Antibody business |
| Zdroj: | Cancer gene therapy. 16(7) |
| ISSN: | 1476-5500 |
| Popis: | 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 microg 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-gamma (IFN-gamma) 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-gamma 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. |
| Databáze: | OpenAIRE |
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