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Induction of Primary NY-ESO-1 Immunity: CD8+ T Lymphocyte and Antibody Responses in Peptide-Vaccinated Patients with NY-ESO-1+ Cancers
Elke Jager, Sacha Gnjatic, Yasuhiro Nagata, Elisabeth Stockert, Dirk Jager, Julia Karbach, Antje Neumann, Julia Rieckenberg, Yao-Tseng Chen, Gerd Ritter, Eric Hoffman, Michael Arand, Lloyd J. Old and Alexander Knuth
Proceedings of the National Academy of Sciences of the United States of America
Vol. 97, No. 22 (Oct. 24, 2000), pp. 12198-12203
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/123814
Page Count: 6
You can always find the topics here!Topics: Vaccination, T lymphocytes, Reactivity, Tumors, Antibodies, Immunization, Melanoma, Lesions, Cytotoxicity, Disease progression
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Cancer-testis antigen NY-ESO-1 is one of the most immunogenic tumor antigens defined to date. Spontaneous humoral and CD8+ T-cell responses to NY-ESO-1 are detected in 40-50% of patients with advanced NY-ESO-1-expressing tumors. A clinical trial was initiated to study the immunological effects of intradermal vaccination with 3 HLA-A2-binding NY-ESO-1 peptides in 12 patients with metastatic NY-ESO-1-expressing cancers. Seven patients were NY-ESO-1 serum antibody negative, and five patients were NY-ESO-1 serum antibody positive at the outset of the study. Primary peptide-specific CD8+ T-cell reactions and delayed-type hypersensitivity responses were generated in four of seven NY-ESO-1 antibody-negative patients. Induction of a specific CD8+ T-cell response to NY-ESO-1 in immunized antibody-negative patients was associated with disease stabilization and objective regression of single metastases. NY-ESO-1 antibody-positive patients did not develop significant changes in baseline NY-ESO-1-specific T-cell reactivity. However, stabilization of disease and regression of individual metastases were observed in three of five immunized patients. These results demonstrate that primary NY-ESO-1-specific CD8+ T-cell responses can be induced by intradermal immunization with NY-ESO-1 peptides, and that immunization with NY-ESO-1 may have the potential to alter the natural course of NY-ESO-1-expressing tumors.
Proceedings of the National Academy of Sciences of the United States of America © 2000 National Academy of Sciences