Vaccination for Malignant Melanoma: Recent Developments

The identification of tumor-associated antigens recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer immunotherapy. Different categories of cancer-associated antigens have been described as targets for CD8+ T cells in vitro and in vivo: (1) 'cancer-testis' (CT) antigens expressed in different tumors and normal testis; (2) melanocyte differentiation antigens; (3) point mutations of normal genes; (4) antigens that are overexpressed in malignant tissues, and (5) viral antigens. Clinical trials with antigenic peptides have been initiated to induce specific immunological responses in vivo. Immunological and clinical parameters for the assessment of peptide-specific reactions have been defined: DTH, CD8+ T cell, autoimmune and tumor regression responses. Preliminary results show that tumor-associated peptides alone elicit specific DTH and CD8+ T cell responses associated with tumor regression after intradermal vaccination. Granulocyte macrophage colony-stimulating factor has been shown to enhance peptide-specific immune reactions by amplification of dermal antigen-presenting dendritic cells. Complete tumor regressions have been observed after the induction of CD8+ T cell responses by peptide immunization. Based on these results, active immunotherapy with tumor-associated antigens may be a promising approach for patients in adjuvant treatment situations, who are at high risk for tumor recurrence. Recently, a strategy utilizing spontaneous antibody responses to tumor-associated antigens (SEREX) has led to the identification of a new CT antigen, NY-ESO-1. NY-ESO-1-specific spontaneous humoral and cellular immune responses were found in approximately 50% of patients with NY-ESO-1-positive tumors. Clinical studies have been initiated to evaluate the immunological effects of immunization with NY-ESO-1 peptides in cancer patients with detectable or absent immunity against NY-ESO-1.