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Critical Reviews™ in Immunology
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ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v18.i1-2.70
pages 55-63

Recognition of Melanoma-Derived Antigens by CTL: Possible Mechanisms Involved in Down-Regulating Anti-Tumor T-Cell Reactivity

Licia Rivoltini
Istituto Nazionale dei Tumori, Milano, Italy
Douglas J. Loftus
laboratory of Cell Biology ,National Cancer Institute, NIH, Bethesda MD, USA
Paola Squarcina
Istituto Nazionale dei Tumori, Milano, Italy
Chiara Castelli
Istituto Nazionale dei Tumori, Milano, Italy
Francesca Rini
Istituto Nazionale dei Tumori, Milano, Italy
Flavio Arienti
Istituto Nazionale dei Tumori, Milano, Italy
Filiberto Belli
Istituto Nazionale dei Tumori, Milano, Italy
Francesco M. Marincola
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
Carsten Geisler
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark
Alessandro Borsatti
lstituto "M. Negri", Milano, Italy
Ettore Appella
laboratory of Cell Biology ,National Cancer Institute, NIH, Bethesda MD, USA
Giorgio Parmiani
Istituto Nazionale dei Tumori, Milano, Italy

SINOPSIS

Several T cell-recognized epitopes presented by melanoma cells have been identified recently. Despite the large array of epitopes potentially available for clinical use, it is still unclear which of these antigens could be effective in mediating anti-tumor responses when used as a vaccine. Preliminary studies showed that immunization of melanoma patients with epitopes derived from proteins of the MAGE family may result in significant clinical regressions. However, no sign of systemic immunization could be observed in peripheral blood of treated patients. Conversely, significant immunization (detected as increased antigen-specific CTL activity in peripheral blood) was obtained by vaccinating HLA-A2.1+ melanoma patients with the immunodominant epitope (residues 27-35) of the differentiation antigen MART-1, but this immunization was not accompanied by a significant clinical response. To implement immunotherapeuties capable of significantly impacting disease outcome, it is necessary to identify the potential mechanisms responsible for the failure of some antigens to mediate significant anti-tumor responses in vivo. In the case of the MART-127.35 epitope, we hypothesize that one of these mechanisms may be related to the existence of natural analogs of this peptide in other human normal proteins.