Monitoring CD8 T cell responses to NY-ESO-1: Correlation of humoral and cellular immune responses

Elke Jäger, Yasuhiro Nagata, Sacha Gnjatic, Hisashi Wada, Elisabeth Stockert, Julia Karbach, P. Rod Dunbar, Sang Yull Lee, Achim Jungbluth, Dirk Jäger, Michael Arand, Gerd Ritter, Vincenzo Cerundolo, Bo Dupont, Yao Tseng Chen, Lloyd J. Old, Alexander Knuth

Research output: Contribution to journalArticlepeer-review

366 Scopus citations

Abstract

NY-ESO-1, a member of the cancer-testis family of antigens, is expressed in a subset of a broad range of different human tumor types. Patients with advanced NY-ESO-1-expressing tumors frequently develop humoral immunity to NY-ESO-1, and three HLA A2-restricted peptides were defined previously as targets for cytotoxic CD8+ T cells in a melanoma patient with NY-ESO-1 antibody. The objectives of the present study were (i) to develop enzyme- linked immunospot (ELISPOT) and tetramer assays to measure CD8+ T cell responses to NY-ESO-1, (ii) to determine the frequency of CD8+ T cell responses to NY-ESO-1 in a series of HLA-A2 patients with NY-ESO-1 expressing tumors, (ii) to determine the relation between CD8+ T cell and humoral immune responses to NY-ESO-1, and (iv) to compare results of NY-ESO-1 ELISPOT assays performed independently in two laboratories with T cells from the same patients. NY-ESO-1 ELISPOT and tetramer assays with excellent sensitivity, specificity, and reproducibility have been developed and found to correlate with cytotoxicity assays. CD8+ T cell responses to HLA-A2-restricted NY-ESO- 1 peptides were detected in 10 of 11 patients with NY-ESO-1 antibody, but not in patients lacking antibody or in patients with NY-ESO-1-negative tumors. The results of ELISPOT assays were concordant in the two laboratories, providing the basis for standardized monitoring of T cell responses in patients receiving NY-ESO-1 vaccines.

Original languageEnglish
Pages (from-to)4760-4765
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number9
DOIs
StatePublished - 25 Apr 2000
Externally publishedYes

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