Strategy for Monitoring T Cell Responses to NY-ESO-1 in Patients with Any HLA Class I Allele

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 20; pp. 10917 - 10922
• Main Authors: Gnjatic, Sacha, Nagata, Yasuhiro, Jager, Elke, Stockert, Elisabeth, Shankara, Srinivas, Roberts, Bruce L., Mazzara, Gail P., Lee, Sang Yull, Dunbar, P. Rod, Dupont, Bo, Cerundolo, Vincenzo, Ritter, Gerd, Chen, Yao-Tseng, Knuth, Alexander, Old, Lloyd J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 26.09.2000; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Adenovirus; Adenoviruses; Alleles; Antigen Presentation; Antigens, Neoplasm - immunology; B lymphocytes; Biological Sciences; Blood; Cancer; CD8-Positive T-Lymphocytes - immunology; Cell lines; Cytotoxicity, Immunologic; Epitopes; Gene Transfer Techniques; Genetic Vectors; histocompatibility antigen HLA; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; histocompatibility locus HLA; HLA antigens; Humans; Immunology; Melanoma; Membrane Proteins; NY-ESO-1 antigen; Proteins - genetics; Proteins - immunology; T lymphocytes; Tumors; Vaccinia virus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.97.20.10917

NY-ESO-1 elicits frequent antibody responses in cancer patients, accompanied by strong CD8+T cell responses against HLA-A2-restricted epitopes. To broaden the range of cancer patients who can be assessed for immunity to NY-ESO-1, a general method was devised to detect T cell reactivity independent of prior characterization of epitopes. A recombinant adenoviral vector encoding the full cDNA sequence of NY-ESO-1 was used to transduce CD8-depleted peripheral blood lymphocytes as antigen-presenting cells. These modified antigen-presenting cells were then used to restimulate memory effector cells against NY-ESO-1 from the peripheral blood of cancer patients. Specific CD8+T cells thus sensitized were assayed on autologous B cell targets infected with a recombinant vaccinia virus encoding NY-ESO-1. Strong polyclonal responses were observed against NY-ESO-1 in antibody-positive patients, regardless of their HLA profile. Because the vectors do not cross-react immunologically, only responses to NY-ESO-1 were detected. The approach described here allows monitoring of CD8+T cell responses to NY-ESO-1 in the context of various HLA alleles and has led to the definition of NY-ESO-1 peptides presented by HLA-Cw3 and HLA-Cw6 molecules.