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

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, (iii) 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.

• Authors: E Jäger, Y Nagata, S Gnjatic, H Wada, E Stockert, J Karbach, P R Dunbar, S Y Lee, A Jungbluth, D Jäger, M Arand, G Ritter, V Cerundolo, B Dupont, Y T Chen, L J Old, A Knuth
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 97 Issue 9 Pg. 4760-5 (Apr 25 2000) ISSN: 0027-8424 [Print] United States
• PMID: 10781081 (Publication Type: Journal Article)

Chemical References

• Antigens, Neoplasm
• CTAG1B protein, human
• HLA-A2 Antigen
• Membrane Proteins
• Peptide Fragments
• Proteins
• RNA, Messenger

Topics

• Antibody Formation (drug effects)
• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Cells, Cultured
• Cytotoxicity, Immunologic
• Enzyme-Linked Immunosorbent Assay
• HLA-A2 Antigen (chemistry, immunology)
• Histocompatibility Testing
• Humans
• Immunity, Cellular (drug effects)
• Melanoma (immunology)
• Membrane Proteins
• Peptide Fragments (immunology, pharmacology)
• Proteins (genetics, immunology, pharmacology)
• RNA, Messenger (genetics)