Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses.
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.
Jäger
E
E
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany. 100333.1434@compuserve.com
Nagata
Y
Y
Gnjatic
S
S
Wada
H
H
Stockert
E
E
Karbach
J
J
Dunbar
P R
PR
Lee
S Y
SY
Jungbluth
A
A
Jäger
D
D
Arand
M
M
Ritter
G
G
Cerundolo
V
V
Dupont
B
B
Chen
Y T
YT
Old
L J
LJ
Knuth
A
A
D000917:Antibody Formation / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008545:Melanoma / Q000276:immunology*; D008565:Membrane Proteins; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D010446:Peptide Fragments; D011506:Proteins; D012333:RNA, Messenger