Tum-or-reactive T helper lymphocytes recognize a promiscuous MAGE-A3 epitope presented by various major histocompatibility complex class II alleles

Hiroya Kobayashi, Yongsheng Song, Dave S.B. Hoon, Ettore Appella, Esteban Celis

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The development of effective T cell-based immunotherapy for cancer requires the identification of antigens capable of inducing both CTL and T helper immune responses. Although CTLs will participate in the anti-tumor response mainly by exerting their lytic activity on the tumor cells, helper T lymphocytes will be critical for the induction and maintenance of the CTLs. Thus, effective subunit therapeutic vaccines should include both CTL and T helper epitopes from antigens expressed on the tumor cells. The product of the MAGE-A3 gene is an attractive candidate for tumor immunotherapy because it is expressed in the majority of melanomas and in a great proportion of other solid tumors. Although numerous CTL epitopes for the MAGE-A3 antigen have been reported, only a few have been described for helper T cells. Here we show that a synthetic peptide derived from the MAGE-A3 sequence (MAGE-A3146-160) was effective in inducing in vitro T helper responses in the context of HLA-DR4 and HLA-DR7 alleles. Most significantly, the peptide-reactive helper T lymphocytes were capable of recognizing various forms of MAGE-A3 antigen (tumor cell lysates, dead/apoptotic tumor cells, or recombinant MAGE-A3 protein), indicating that the T-cell epitope represented by peptide MAGE-A3146-160 is naturally processed by antigen-presenting cells. These studies are relevant for the design of multi-epitope vaccines for treating MAGE-A3-expressing tumors through the simultaneous stimulation of CTL and T helper lymphocytes.

Original languageEnglish (US)
Pages (from-to)4773-4778
Number of pages6
JournalCancer Research
Volume61
Issue number12
StatePublished - Jun 15 2001
Externally publishedYes

Fingerprint

Helper-Inducer T-Lymphocytes
Major Histocompatibility Complex
Epitopes
Alleles
Neoplasms
Antigens
Immunotherapy
Peptides
HLA-DR7 Antigen
HLA-DR4 Antigen
Subunit Vaccines
T-Lymphocyte Epitopes
Neoplasm Antigens
Antigen-Presenting Cells
Melanoma
Vaccines
Maintenance
T-Lymphocytes
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tum-or-reactive T helper lymphocytes recognize a promiscuous MAGE-A3 epitope presented by various major histocompatibility complex class II alleles. / Kobayashi, Hiroya; Song, Yongsheng; Hoon, Dave S.B.; Appella, Ettore; Celis, Esteban.

In: Cancer Research, Vol. 61, No. 12, 15.06.2001, p. 4773-4778.

Research output: Contribution to journalArticle

Kobayashi, Hiroya ; Song, Yongsheng ; Hoon, Dave S.B. ; Appella, Ettore ; Celis, Esteban. / Tum-or-reactive T helper lymphocytes recognize a promiscuous MAGE-A3 epitope presented by various major histocompatibility complex class II alleles. In: Cancer Research. 2001 ; Vol. 61, No. 12. pp. 4773-4778.
@article{3ce4d160c9b74299a3971f7d99c856d8,
title = "Tum-or-reactive T helper lymphocytes recognize a promiscuous MAGE-A3 epitope presented by various major histocompatibility complex class II alleles",
abstract = "The development of effective T cell-based immunotherapy for cancer requires the identification of antigens capable of inducing both CTL and T helper immune responses. Although CTLs will participate in the anti-tumor response mainly by exerting their lytic activity on the tumor cells, helper T lymphocytes will be critical for the induction and maintenance of the CTLs. Thus, effective subunit therapeutic vaccines should include both CTL and T helper epitopes from antigens expressed on the tumor cells. The product of the MAGE-A3 gene is an attractive candidate for tumor immunotherapy because it is expressed in the majority of melanomas and in a great proportion of other solid tumors. Although numerous CTL epitopes for the MAGE-A3 antigen have been reported, only a few have been described for helper T cells. Here we show that a synthetic peptide derived from the MAGE-A3 sequence (MAGE-A3146-160) was effective in inducing in vitro T helper responses in the context of HLA-DR4 and HLA-DR7 alleles. Most significantly, the peptide-reactive helper T lymphocytes were capable of recognizing various forms of MAGE-A3 antigen (tumor cell lysates, dead/apoptotic tumor cells, or recombinant MAGE-A3 protein), indicating that the T-cell epitope represented by peptide MAGE-A3146-160 is naturally processed by antigen-presenting cells. These studies are relevant for the design of multi-epitope vaccines for treating MAGE-A3-expressing tumors through the simultaneous stimulation of CTL and T helper lymphocytes.",
author = "Hiroya Kobayashi and Yongsheng Song and Hoon, {Dave S.B.} and Ettore Appella and Esteban Celis",
year = "2001",
month = "6",
day = "15",
language = "English (US)",
volume = "61",
pages = "4773--4778",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - Tum-or-reactive T helper lymphocytes recognize a promiscuous MAGE-A3 epitope presented by various major histocompatibility complex class II alleles

AU - Kobayashi, Hiroya

AU - Song, Yongsheng

AU - Hoon, Dave S.B.

AU - Appella, Ettore

AU - Celis, Esteban

PY - 2001/6/15

Y1 - 2001/6/15

N2 - The development of effective T cell-based immunotherapy for cancer requires the identification of antigens capable of inducing both CTL and T helper immune responses. Although CTLs will participate in the anti-tumor response mainly by exerting their lytic activity on the tumor cells, helper T lymphocytes will be critical for the induction and maintenance of the CTLs. Thus, effective subunit therapeutic vaccines should include both CTL and T helper epitopes from antigens expressed on the tumor cells. The product of the MAGE-A3 gene is an attractive candidate for tumor immunotherapy because it is expressed in the majority of melanomas and in a great proportion of other solid tumors. Although numerous CTL epitopes for the MAGE-A3 antigen have been reported, only a few have been described for helper T cells. Here we show that a synthetic peptide derived from the MAGE-A3 sequence (MAGE-A3146-160) was effective in inducing in vitro T helper responses in the context of HLA-DR4 and HLA-DR7 alleles. Most significantly, the peptide-reactive helper T lymphocytes were capable of recognizing various forms of MAGE-A3 antigen (tumor cell lysates, dead/apoptotic tumor cells, or recombinant MAGE-A3 protein), indicating that the T-cell epitope represented by peptide MAGE-A3146-160 is naturally processed by antigen-presenting cells. These studies are relevant for the design of multi-epitope vaccines for treating MAGE-A3-expressing tumors through the simultaneous stimulation of CTL and T helper lymphocytes.

AB - The development of effective T cell-based immunotherapy for cancer requires the identification of antigens capable of inducing both CTL and T helper immune responses. Although CTLs will participate in the anti-tumor response mainly by exerting their lytic activity on the tumor cells, helper T lymphocytes will be critical for the induction and maintenance of the CTLs. Thus, effective subunit therapeutic vaccines should include both CTL and T helper epitopes from antigens expressed on the tumor cells. The product of the MAGE-A3 gene is an attractive candidate for tumor immunotherapy because it is expressed in the majority of melanomas and in a great proportion of other solid tumors. Although numerous CTL epitopes for the MAGE-A3 antigen have been reported, only a few have been described for helper T cells. Here we show that a synthetic peptide derived from the MAGE-A3 sequence (MAGE-A3146-160) was effective in inducing in vitro T helper responses in the context of HLA-DR4 and HLA-DR7 alleles. Most significantly, the peptide-reactive helper T lymphocytes were capable of recognizing various forms of MAGE-A3 antigen (tumor cell lysates, dead/apoptotic tumor cells, or recombinant MAGE-A3 protein), indicating that the T-cell epitope represented by peptide MAGE-A3146-160 is naturally processed by antigen-presenting cells. These studies are relevant for the design of multi-epitope vaccines for treating MAGE-A3-expressing tumors through the simultaneous stimulation of CTL and T helper lymphocytes.

UR - http://www.scopus.com/inward/record.url?scp=0035874608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035874608&partnerID=8YFLogxK

M3 - Article

C2 - 11406551

AN - SCOPUS:0035874608

VL - 61

SP - 4773

EP - 4778

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 12

ER -