Induction of Primary NY-ESO-1 Immunity: CD8+ T Lymphocyte and Antibody Responses in Peptide-Vaccinated Patients with NY-ESO-1+ Cancers

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 22; pp. 12198 - 12203
• Main Authors: Jager, Elke, Gnjatic, Sacha, Nagata, Yasuhiro, Stockert, Elisabeth, Jager, Dirk, Karbach, Julia, Neumann, Antje, Rieckenberg, Julia, Chen, Yao-Tseng, Ritter, Gerd, Hoffman, Eric, Arand, Michael, Old, Lloyd J., Knuth, Alexander
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 24.10.2000; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Amino Acid Sequence; Antibodies; Antibodies, Neoplasm - biosynthesis; Antigens, Neoplasm - immunology; Biological Sciences; Cancer; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cells; Clinical trials; Cytotoxicity; Cytotoxicity, Immunologic; Disease progression; Humans; Hypersensitivity, Delayed; Immunization; Lesions; Male; Melanoma; Membrane Proteins; NY-ESO-1 antigen; Peptides; Peptides - administration & dosage; Peptides - immunology; Proteins - immunology; Reactivity; T lymphocytes; Testis - immunology; Tumors; Vaccination
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.220413497

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.