title: Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. s-gnjatic@ski.mskcc.org
authors.forename: S
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Y
authors.initials: Y
authors.lastname: Nagata
authors.forename: E
authors.initials: E
authors.lastname: Jager
authors.forename: E
authors.initials: E
authors.lastname: Stockert
authors.forename: S
authors.initials: S
authors.lastname: Shankara
authors.forename: B L
authors.initials: BL
authors.lastname: Roberts
authors.forename: G P
authors.initials: GP
authors.lastname: Mazzara
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.forename: P R
authors.initials: PR
authors.lastname: Dunbar
authors.forename: B
authors.initials: B
authors.lastname: Dupont
authors.forename: V
authors.initials: V
authors.lastname: Cerundolo
authors.forename: G
authors.initials: G
authors.lastname: Ritter
authors.forename: Y T
authors.initials: YT
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Knuth
authors.forename: L J
authors.initials: LJ
authors.lastname: Old
mesh_terms: D000483:Alleles; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011506:Proteins