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

Research output: Contribution to journalArticle

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

Fingerprint

MART-1 Antigen
Tumor-Infiltrating Lymphocytes
T-Lymphoid Precursor Cells
Neoplasm Metastasis
Melanoma-Specific Antigens
T-Lymphocytes
Neoplasms
Differentiation Antigens
Epitopes
T Lymphocyte Differentiation Antigens
Adoptive Transfer
Melanoma
Cytokines

Keywords

  • Immunotherapy
  • Melanoma antigens
  • Tumor-specific antigens

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes. / Seiter, Simone; Monsurro, Vladia; Nielsen, Mai Britt; Wang, Ena; Provenzano, Maurizio; Wunderlich, John R.; Rosenberg, Steven A.; Marincola, Francesco M.

In: Journal of Immunotherapy, Vol. 25, No. 3, 2002, p. 252-263.

Research output: Contribution to journalArticle

Seiter, S, Monsurro, V, Nielsen, MB, Wang, E, Provenzano, M, Wunderlich, JR, Rosenberg, SA & Marincola, FM 2002, 'Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes', Journal of Immunotherapy, vol. 25, no. 3, pp. 252-263. https://doi.org/10.1097/00002371-200205000-00008
Seiter, Simone ; Monsurro, Vladia ; Nielsen, Mai Britt ; Wang, Ena ; Provenzano, Maurizio ; Wunderlich, John R. ; Rosenberg, Steven A. ; Marincola, Francesco M. / Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes. In: Journal of Immunotherapy. 2002 ; Vol. 25, No. 3. pp. 252-263.
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AU - Nielsen, Mai Britt

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AU - Provenzano, Maurizio

AU - Wunderlich, John R.

AU - Rosenberg, Steven A.

AU - Marincola, Francesco M.

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AB - 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.

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