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Immunologic and Clinical Outcomes of a Randomized Phase II Trial of Two Multipeptide Vaccines for Melanoma in the Adjuvant Setting

Authors' Affiliations: Departments of ¹ Surgery and ² Public Health Sciences; ³ Cancer Center; and ⁴ Division of Hematology-Oncology, Department of Medicine; and Departments of ⁵ Pathology and ⁶ Radiology, University of Virginia, Charlottesville, Virginia

Requests for reprints: Craig L. Slingluff, Jr., Department of Surgery, Human Immune Therapy Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA 22908. Phone: 434-243-2611; Fax: 434-982-3276; E-mail: cls8h{at}virginia.edu.

Purpose: Human melanoma cells express shared antigens recognized by CD8⁺ T lymphocytes, the most common of which are melanocytic differentiation proteins and cancer-testis antigens. However, peptide vaccines for melanoma usually target only one or two MHC class I–associated peptide antigens. Because melanomas commonly evade immune recognition by selective antigen loss, optimization of melanoma vaccines may require development of more complex multipeptide vaccines.

Experimental Design: In a prospective randomized clinical trial, we have evaluated the safety and immunogenicity of a vaccine containing a mixture of 12 peptides from melanocytic differentiation proteins and cancer-testis antigens, designed for human leukocyte antigen types that represent 80% of the melanoma patient population. This was compared with a four-peptide vaccine with only melanocytic differentiation peptides. Immune responses were assessed in peripheral blood and in vaccine-draining lymph nodes.

Results: These data show that (a) the 12-peptide mixture is immunogenic in all treated patients; (b) immunogenicity of individual peptides is maintained despite competition with additional peptides for binding to MHC molecules; (c) a broader and more robust immune response is induced by vaccination with the more complex 12-peptide mixture; and (d) clinical outcome in this peptide vaccine trial correlates with immune responses measured in the peripheral blood lymphocytes.

Conclusions: These data support continued investigation of complex multipeptide vaccines for melanoma.