Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes

Simone Seiter, Vladia Monsurro, Mai Britt Nielsen, Ena Wang, Maurizio Provenzano, John R. Wunderlich, Steven A. Rosenberg, Francesco M. Marincola

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28 Citations (Scopus)

Abstract

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 21,000/106 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.

Original languageEnglish
Pages (from-to)252-263
Number of pages12
JournalJournal of Immunotherapy
Volume25
Issue number3
DOIs
Publication statusPublished - 2002
Externally publishedYes

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Keywords

  • Immunotherapy
  • Melanoma antigens
  • Tumor-specific antigens

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Seiter, S., Monsurro, V., Nielsen, M. B., Wang, E., Provenzano, M., Wunderlich, J. R., Rosenberg, S. A., & Marincola, F. M. (2002). Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes. Journal of Immunotherapy, 25(3), 252-263. https://doi.org/10.1097/00002371-200205000-00008