Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1

Licia Rivoltini, Yutaka Kawakami, Kazuyasu Sakaguchi, Scott Southwood, Alessandro Sette, Paul F. Robbins, Francesco M. Marincola, Michael L. Salgaller, John R. Yannelli, Ettore Appella, Steven A. Rosenberg

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Abstract

MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-127-35 peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-135-43-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-127-35-specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2+ melanoma patients, as well as from 2 of 4 PBL from HLA-A2+ healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-127-35 peptide. These CTL lines specifically lysed and release cytokines (TNF-α, IFN-γ, and GM-CSF) in response to T2 cells pulsed with MART-127-35, as well as to HLA-A2+ MART-1+ melanoma cells. CTL generated with MART-127-35 also lysed uncultured HLA-A2+ melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-127-35 mediated 25- to 100-fold higher lytic activity than MART-1 -reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-127-35 peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients.

Original languageEnglish
Pages (from-to)2257-2265
Number of pages9
JournalJournal of Immunology
Volume154
Issue number5
Publication statusPublished - 1995
Externally publishedYes

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Tumor-Infiltrating Lymphocytes
HLA-A2 Antigen
Melanoma
Peptides
Neoplasms
Epitopes
T-Lymphocytes
human MAGEA1 protein
In Vitro Techniques
Melanocytes
Granulocyte-Macrophage Colony-Stimulating Factor
Immunotherapy
Interleukin-2
Tissue Donors
Cytokines
Biopsy
Cell Line

ASJC Scopus subject areas

  • Immunology

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Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1. / Rivoltini, Licia; Kawakami, Yutaka; Sakaguchi, Kazuyasu; Southwood, Scott; Sette, Alessandro; Robbins, Paul F.; Marincola, Francesco M.; Salgaller, Michael L.; Yannelli, John R.; Appella, Ettore; Rosenberg, Steven A.

In: Journal of Immunology, Vol. 154, No. 5, 1995, p. 2257-2265.

Research output: Contribution to journalArticle

Rivoltini, L, Kawakami, Y, Sakaguchi, K, Southwood, S, Sette, A, Robbins, PF, Marincola, FM, Salgaller, ML, Yannelli, JR, Appella, E & Rosenberg, SA 1995, 'Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1', Journal of Immunology, vol. 154, no. 5, pp. 2257-2265.
Rivoltini, Licia ; Kawakami, Yutaka ; Sakaguchi, Kazuyasu ; Southwood, Scott ; Sette, Alessandro ; Robbins, Paul F. ; Marincola, Francesco M. ; Salgaller, Michael L. ; Yannelli, John R. ; Appella, Ettore ; Rosenberg, Steven A. / Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1. In: Journal of Immunology. 1995 ; Vol. 154, No. 5. pp. 2257-2265.
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title = "Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1",
abstract = "MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-127-35 peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-135-43-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-127-35-specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2+ melanoma patients, as well as from 2 of 4 PBL from HLA-A2+ healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-127-35 peptide. These CTL lines specifically lysed and release cytokines (TNF-α, IFN-γ, and GM-CSF) in response to T2 cells pulsed with MART-127-35, as well as to HLA-A2+ MART-1+ melanoma cells. CTL generated with MART-127-35 also lysed uncultured HLA-A2+ melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-127-35 mediated 25- to 100-fold higher lytic activity than MART-1 -reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-127-35 peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients.",
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T1 - Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1

AU - Rivoltini, Licia

AU - Kawakami, Yutaka

AU - Sakaguchi, Kazuyasu

AU - Southwood, Scott

AU - Sette, Alessandro

AU - Robbins, Paul F.

AU - Marincola, Francesco M.

AU - Salgaller, Michael L.

AU - Yannelli, John R.

AU - Appella, Ettore

AU - Rosenberg, Steven A.

PY - 1995

Y1 - 1995

N2 - MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-127-35 peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-135-43-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-127-35-specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2+ melanoma patients, as well as from 2 of 4 PBL from HLA-A2+ healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-127-35 peptide. These CTL lines specifically lysed and release cytokines (TNF-α, IFN-γ, and GM-CSF) in response to T2 cells pulsed with MART-127-35, as well as to HLA-A2+ MART-1+ melanoma cells. CTL generated with MART-127-35 also lysed uncultured HLA-A2+ melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-127-35 mediated 25- to 100-fold higher lytic activity than MART-1 -reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-127-35 peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients.

AB - MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-127-35 peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-135-43-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-127-35-specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2+ melanoma patients, as well as from 2 of 4 PBL from HLA-A2+ healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-127-35 peptide. These CTL lines specifically lysed and release cytokines (TNF-α, IFN-γ, and GM-CSF) in response to T2 cells pulsed with MART-127-35, as well as to HLA-A2+ MART-1+ melanoma cells. CTL generated with MART-127-35 also lysed uncultured HLA-A2+ melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-127-35 mediated 25- to 100-fold higher lytic activity than MART-1 -reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-127-35 peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients.

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