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 journalArticlepeer-review

71 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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