Malignant melanoma remains a difficult clinical problem. Chemotherapy is not effective and immunotherapy has long been contemplated as the preferred approach to this disease. Extensive passive and active immunotherapy trials have been conducted. Active vaccination with whole cells or defined antigens, administered with a panoply of techniques to increase immunogenicity, has yielded inconsistent results. The development of antibody-based vaccines has allowed vaccination without the need for tumor tissue material or purified antigens. The idiotype network theory originally proposed by Lindemann and by Jerne provided the basis for the development of anti-idiotype (anti-Id) antibody vaccines, which mimic the internal image of the epitope targeted for immunization. Preclinical and phase I clinical data are available for various malignancies. In melanoma, some of the anti-Id vaccines have targeted gangliosides. One of these vaccines, TriGem, has been successful in generating a robust and specific humoral immunity in melanoma patients. Phase II data suggest this anti-Id vaccine has clinical activity.
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