Recognition of Multiple Epitopes in the Human Melanoma Antigen gplOO by Peripheral Blood Lymphocytes Stimulated in Vitro with Synthetic Peptides

Michael L. Salgaller, Alireza Afshar, Francesco M. Marincola, Licia Rivoltini, Yutaka Kawakami, Steven A. Rosenberg

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

gplOO is a melanocyte lineage-specific antigen recognized by tumor-infiltrating lymphocytes whose adoptive transfer has been associated with tumor regression in patients with metastatic melanoma. The peripheral blood mononuclear cells of five melanoma patients were sensitized in vitro with synthetic peptides to elicit antigen-specific cytotoxic T lymphocyte (CTL) lines against four gplOO epitopes. These epitope-specific CTL lines were generated following weekly in vitro stimulation with the synthetic decamer G10476 (V-L-Y-R-Y-G-S-F-S-V) or the nonamers G9280 (Y-L-E-P-G-P-V-T-A), G9154 (K-T-W-G-Q-Y-W-Q-V), or G9209 (I-T-D-Q-V-P-F-S-V) pulsed onto autologous irradiated peripheral blood mononuclear cells. These lines grew as long as 4 months in culture in low-dose interleukin 2 (30 IU/ml) and exhibited antigen-specific, MHC class I-restricted lysis of peptide-pulsed T2 cells and HLA-A2+, gplOO+ established melanoma cell lines. G10476- and G9280-specific CTLs demonstrated specific release of granulocyte-macrophage-colony-stimnlating factor and tumor necrosis factor a in response to T2 cells pulsed with relevant peptide, as well as to gplOO+ melanoma cell lines. These results demonstrate that several peptides derived from the gplOO protein are presented on the surface of melanoma cells and are sufficiently immunogenic to generate, in vitro, potent CTLs capable of cytolysis and the secretion of cytokines. Therefore, for HLA-A2+ melanoma patients, these and possibly other gplOO peptides could represent good candidates for antigen-specific immunotherapy either singly or in a multivalent regimen.

Original languageEnglish
Pages (from-to)4972-4979
Number of pages8
JournalCancer Research
Volume55
Issue number21
Publication statusPublished - 1995 Nov 1
Externally publishedYes

Fingerprint

Melanoma-Specific Antigens
Epitopes
Melanoma
Lymphocytes
Peptides
HLA-A2 Antigen
Antigens
Cytotoxic T-Lymphocytes
Blood Cells
Tumor-Infiltrating Lymphocytes
Cell Line
Adoptive Transfer
Melanocytes
Granulocytes
Immunotherapy
Interleukin-2
In Vitro Techniques
Tumor Necrosis Factor-alpha
Macrophages
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Salgaller, M. L., Afshar, A., Marincola, F. M., Rivoltini, L., Kawakami, Y., & Rosenberg, S. A. (1995). Recognition of Multiple Epitopes in the Human Melanoma Antigen gplOO by Peripheral Blood Lymphocytes Stimulated in Vitro with Synthetic Peptides. Cancer Research, 55(21), 4972-4979.

Recognition of Multiple Epitopes in the Human Melanoma Antigen gplOO by Peripheral Blood Lymphocytes Stimulated in Vitro with Synthetic Peptides. / Salgaller, Michael L.; Afshar, Alireza; Marincola, Francesco M.; Rivoltini, Licia; Kawakami, Yutaka; Rosenberg, Steven A.

In: Cancer Research, Vol. 55, No. 21, 01.11.1995, p. 4972-4979.

Research output: Contribution to journalArticle

Salgaller, ML, Afshar, A, Marincola, FM, Rivoltini, L, Kawakami, Y & Rosenberg, SA 1995, 'Recognition of Multiple Epitopes in the Human Melanoma Antigen gplOO by Peripheral Blood Lymphocytes Stimulated in Vitro with Synthetic Peptides', Cancer Research, vol. 55, no. 21, pp. 4972-4979.
Salgaller ML, Afshar A, Marincola FM, Rivoltini L, Kawakami Y, Rosenberg SA. Recognition of Multiple Epitopes in the Human Melanoma Antigen gplOO by Peripheral Blood Lymphocytes Stimulated in Vitro with Synthetic Peptides. Cancer Research. 1995 Nov 1;55(21):4972-4979.
Salgaller, Michael L. ; Afshar, Alireza ; Marincola, Francesco M. ; Rivoltini, Licia ; Kawakami, Yutaka ; Rosenberg, Steven A. / Recognition of Multiple Epitopes in the Human Melanoma Antigen gplOO by Peripheral Blood Lymphocytes Stimulated in Vitro with Synthetic Peptides. In: Cancer Research. 1995 ; Vol. 55, No. 21. pp. 4972-4979.
@article{ac49f08bb51a4636b984dc7989ff317a,
title = "Recognition of Multiple Epitopes in the Human Melanoma Antigen gplOO by Peripheral Blood Lymphocytes Stimulated in Vitro with Synthetic Peptides",
abstract = "gplOO is a melanocyte lineage-specific antigen recognized by tumor-infiltrating lymphocytes whose adoptive transfer has been associated with tumor regression in patients with metastatic melanoma. The peripheral blood mononuclear cells of five melanoma patients were sensitized in vitro with synthetic peptides to elicit antigen-specific cytotoxic T lymphocyte (CTL) lines against four gplOO epitopes. These epitope-specific CTL lines were generated following weekly in vitro stimulation with the synthetic decamer G10476 (V-L-Y-R-Y-G-S-F-S-V) or the nonamers G9280 (Y-L-E-P-G-P-V-T-A), G9154 (K-T-W-G-Q-Y-W-Q-V), or G9209 (I-T-D-Q-V-P-F-S-V) pulsed onto autologous irradiated peripheral blood mononuclear cells. These lines grew as long as 4 months in culture in low-dose interleukin 2 (30 IU/ml) and exhibited antigen-specific, MHC class I-restricted lysis of peptide-pulsed T2 cells and HLA-A2+, gplOO+ established melanoma cell lines. G10476- and G9280-specific CTLs demonstrated specific release of granulocyte-macrophage-colony-stimnlating factor and tumor necrosis factor a in response to T2 cells pulsed with relevant peptide, as well as to gplOO+ melanoma cell lines. These results demonstrate that several peptides derived from the gplOO protein are presented on the surface of melanoma cells and are sufficiently immunogenic to generate, in vitro, potent CTLs capable of cytolysis and the secretion of cytokines. Therefore, for HLA-A2+ melanoma patients, these and possibly other gplOO peptides could represent good candidates for antigen-specific immunotherapy either singly or in a multivalent regimen.",
author = "Salgaller, {Michael L.} and Alireza Afshar and Marincola, {Francesco M.} and Licia Rivoltini and Yutaka Kawakami and Rosenberg, {Steven A.}",
year = "1995",
month = "11",
day = "1",
language = "English",
volume = "55",
pages = "4972--4979",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "21",

}

TY - JOUR

T1 - Recognition of Multiple Epitopes in the Human Melanoma Antigen gplOO by Peripheral Blood Lymphocytes Stimulated in Vitro with Synthetic Peptides

AU - Salgaller, Michael L.

AU - Afshar, Alireza

AU - Marincola, Francesco M.

AU - Rivoltini, Licia

AU - Kawakami, Yutaka

AU - Rosenberg, Steven A.

PY - 1995/11/1

Y1 - 1995/11/1

N2 - gplOO is a melanocyte lineage-specific antigen recognized by tumor-infiltrating lymphocytes whose adoptive transfer has been associated with tumor regression in patients with metastatic melanoma. The peripheral blood mononuclear cells of five melanoma patients were sensitized in vitro with synthetic peptides to elicit antigen-specific cytotoxic T lymphocyte (CTL) lines against four gplOO epitopes. These epitope-specific CTL lines were generated following weekly in vitro stimulation with the synthetic decamer G10476 (V-L-Y-R-Y-G-S-F-S-V) or the nonamers G9280 (Y-L-E-P-G-P-V-T-A), G9154 (K-T-W-G-Q-Y-W-Q-V), or G9209 (I-T-D-Q-V-P-F-S-V) pulsed onto autologous irradiated peripheral blood mononuclear cells. These lines grew as long as 4 months in culture in low-dose interleukin 2 (30 IU/ml) and exhibited antigen-specific, MHC class I-restricted lysis of peptide-pulsed T2 cells and HLA-A2+, gplOO+ established melanoma cell lines. G10476- and G9280-specific CTLs demonstrated specific release of granulocyte-macrophage-colony-stimnlating factor and tumor necrosis factor a in response to T2 cells pulsed with relevant peptide, as well as to gplOO+ melanoma cell lines. These results demonstrate that several peptides derived from the gplOO protein are presented on the surface of melanoma cells and are sufficiently immunogenic to generate, in vitro, potent CTLs capable of cytolysis and the secretion of cytokines. Therefore, for HLA-A2+ melanoma patients, these and possibly other gplOO peptides could represent good candidates for antigen-specific immunotherapy either singly or in a multivalent regimen.

AB - gplOO is a melanocyte lineage-specific antigen recognized by tumor-infiltrating lymphocytes whose adoptive transfer has been associated with tumor regression in patients with metastatic melanoma. The peripheral blood mononuclear cells of five melanoma patients were sensitized in vitro with synthetic peptides to elicit antigen-specific cytotoxic T lymphocyte (CTL) lines against four gplOO epitopes. These epitope-specific CTL lines were generated following weekly in vitro stimulation with the synthetic decamer G10476 (V-L-Y-R-Y-G-S-F-S-V) or the nonamers G9280 (Y-L-E-P-G-P-V-T-A), G9154 (K-T-W-G-Q-Y-W-Q-V), or G9209 (I-T-D-Q-V-P-F-S-V) pulsed onto autologous irradiated peripheral blood mononuclear cells. These lines grew as long as 4 months in culture in low-dose interleukin 2 (30 IU/ml) and exhibited antigen-specific, MHC class I-restricted lysis of peptide-pulsed T2 cells and HLA-A2+, gplOO+ established melanoma cell lines. G10476- and G9280-specific CTLs demonstrated specific release of granulocyte-macrophage-colony-stimnlating factor and tumor necrosis factor a in response to T2 cells pulsed with relevant peptide, as well as to gplOO+ melanoma cell lines. These results demonstrate that several peptides derived from the gplOO protein are presented on the surface of melanoma cells and are sufficiently immunogenic to generate, in vitro, potent CTLs capable of cytolysis and the secretion of cytokines. Therefore, for HLA-A2+ melanoma patients, these and possibly other gplOO peptides could represent good candidates for antigen-specific immunotherapy either singly or in a multivalent regimen.

UR - http://www.scopus.com/inward/record.url?scp=0028871599&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028871599&partnerID=8YFLogxK

M3 - Article

VL - 55

SP - 4972

EP - 4979

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 21

ER -