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Peptide vaccination of patients with metastatic melanoma: improved clinical outcome in patients demonstrating effective immunization.

Author(s): Markovic SN, Suman VJ, Ingle JN, Kaur JS, Pitot HC, Loprinzi CL, Rao RD, Creagan ET, Pittelkow MR, Allred JB, Nevala WK, Celis E

Affiliation(s): Melanoma Study Group of the Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA. markovic.svetomir@mayo.edu

Publication date & source: 2006-08, Am J Clin Oncol., 29(4):352-60.

Publication type: Clinical Trial, Phase II; Randomized Controlled Trial

OBJECTIVES: Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. METHODS: We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 microg); (C) peptides + Montanide ISA-51 + GM-CSF (50 microg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. RESULTS: Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. CONCLUSIONS: The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.

Page last updated: 2006-11-04

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