Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes.
Melanoma differentiation antigens, such as MART-1/MelanA and gp100/PMel17, frequently are observed as targets of tumor infiltrating lymphocytes (TIL) originated from HLA-A*0201-expressing patients with melanoma. Furthermore, particular clinical relevance was attributed to gp100/pMel17 based on the impression that the adoptive transfer of gp100-recognizing TIL was associated with clinical responses in a small group of patients. However, the actual frequency of specific T cells for these melanoma differentiation antigens has never been directly enumerated in ex vivo or in vitro expanded TIL cultures. Here, we enumerated melanoma differentiation antigen-specific T-cell precursor frequency in TIL using tetrameric HLA/epitope complexes, functionally characterizing their responsiveness to cognate epitope by cytokine release assay. T-cell precursor frequencies were enumerated in 11 fresh-tumor preparations and 17 TIL adoptively transferred into patients bearing HLA-A*0201. MART-1 or gp100-specific T cells could be detected respectively in 5 and 2 of the 11 fresh preparations and in 5 and 2 of the 17 adoptively transferred TIL. With one exception, melanoma differentiation antigen-specific T-cell precursor frequency in fresh material and TIL ranged between 5,000 to 21,000/10(6) CD8+ T cells. T-cell precursor frequency was not significantly higher in TIL whose administration was associated with clinical response. These data provide direct enumeration of MART-1/MelanA and gp100/pMel17 reactivity ex vivo and in vitro in the context of HLA-A*0201.
Seiter
Simone
S
Department of Transfusion Medicine, Center for Cancer Research, National Cancer Institute, Building 10, Room 2B42, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Monsurro
Vladia
V
Nielsen
Mai-Britt
MB
Wang
Ena
E
Provenzano
Maurizio
M
Wunderlich
John R
JR
Rosenberg
Steven A
SA
Marincola
Francesco M
FM
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000556:secondary* / Q000628:therapy; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins / Q000276:immunology*; D011506:Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D011506:Proteins; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma