© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 11, 805-818,
June 5, 2002
© 2002 Oxford University Press
REVIEW |
Cancer Immunotherapy With Peptide-Based Vaccines: What Have We Achieved? Where Are We Going?
Affiliations of authors: G. Parmiani, C. Castelli, P. Dalerba, L. Rivoltini (Unit of Immunotherapy of Human Tumors), R. Mortarini, A. Anichini (Unit of Immunobiology of Human Tumors), Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; F. M. Marincola, Immunogenetics Laboratory, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
Correspondence to: Giorgio Parmiani, M.D., Unit of Immunotherapy of Human Tumors, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy (e-mail: parmiani{at}istitutotumori.mi.it).
Many human tumor-associated antigens (TAAs) have recently been identified and molecularly characterized. When bound to major histocompatibility complex molecules, TAA peptides are recognized by T cells. Clinical studies have therefore been initiated to assess the therapeutic potential of active immunization or vaccination with TAA peptides in patients with metastatic cancer. So far, only a limited number of TAA peptides, mostly those recognized by CD8+ T cells in melanoma patients, have been clinically tested. In some clinical trials, partial or complete tumor regression was observed in approximately 10%–30% of patients. No serious side effects have been reported. The clinical responses, however, were often not associated with a detectable T-cell-specific antitumor immune response when patients' T cells were evaluated in ex vivo assays. In this review, we analyze the available human TAA peptides, the potential immunogenicity (i.e., the ability to trigger a tumor-specific T-cell response) of TAA peptides in vitro and ex vivo, and the potential to construct slightly modified forms of TAA peptides that have increased T-cell stimulatory activity. We discuss the available data from clinical trials of TAA peptide-based vaccination (including those that used dendritic cells to present TAA peptides), identify possible reasons for the limited clinical efficacy of these vaccines, and suggest ways to improve the clinical outcome of TAA peptide-based vaccination for cancer patients.
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