title: Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression.
abstract: Four of ten HLA-A2-restricted melanoma specific CTL that were derived from tumor-infiltrating lymphocytes (TIL) and administered to patients recognized the gp100 melanoma Ag and nine of ten recognized the MART-1 Ag. Adoptive transfer of the four gp100-reactive CTL, but not the other TIL, resulted in tumor regression when infused into autologous patients along with IL-2. Tumor regression was thus correlated with the recognition of gp100 by the administered T cells (p = 0.0048). To identify the epitopes recognized by these four gp100-reactive CTL, 169 peptides containing HLA-A2.1 binding motifs were synthesized and screened for their recognition by TIL using cytotoxicity and IFN-gamma release assays. Five gp100 epitopes (two for TIL620, three for TIL660, one for TIL1143, and two for TIL1200) were recognized by CTL derived from different patients. Five of eight HLA-A2 binding melanoma epitopes (five gp100, one MART-1/Melan-A, two tyrosinase) had intermediate binding affinity to HLA-A2.1. These gp100 epitopes may be responsible for mediating tumor rejection in vivo and thus may be useful for the development of immunotherapies for patients with melanoma.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Eliyahu
authors.forename: C
authors.initials: C
authors.lastname: Jennings
authors.forename: K
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: X
authors.initials: X
authors.lastname: Kang
authors.forename: S
authors.initials: S
authors.lastname: Southwood
authors.forename: P F
authors.initials: PF
authors.lastname: Robbins
authors.forename: A
authors.initials: A
authors.lastname: Sette
authors.forename: E
authors.initials: E
authors.lastname: Appella
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000276:immunology*; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010455:Peptides; D058951:gp100 Melanoma Antigen