Induction of anti-tumor cytotoxic T lymphocytes in normal humans using primary cultures and synthetic peptide epitopes

Esteban Celis, Van Tsai, Claire Crimi, Robert Demars, Peggy A. Wentworth, Robert W. Chesnut, Howard M. Grey, Alessandro Sette, Horacio M. Serra

Research output: Contribution to journalArticle

294 Scopus citations

Abstract

Cytotoxic T lymphocytes (CTLs) recognize peptide antigens associated with cell surface major histocompatibility complex (MHC) molecules. The identification of tumor cell-derived peptides capable of eliciting anti- tumor CTL responses would enable the design of antigen-specific immunotherapies. Our strategy to identify such potentially therapeutic peptides relies on selecting high-affinity MHC binders from known tumor- associated antigens. These peptides are subsequently tested for their ability to induce CTLs capable of killing tumor cells. With this strategy, we have identified a nine-residue epitope, derived from the product of the tumor- associated gene MAGE-3, which has the capacity to induce in vitro CTLs that kill melanoma and other tumor cell lines. These results show the primary in vitro induction of tumor-specific human CTLs and illustrate the feasibility of ex vivo antigen-specific approaches to the immunological therapy of cancer.

Original languageEnglish (US)
Pages (from-to)2105-2109
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number6
DOIs
StatePublished - Mar 15 1994

Keywords

  • MAGE antigens
  • major histocompatibility complex antigen-binding peptides
  • melanoma immunity
  • tumor-specific cytotoxic T cells

ASJC Scopus subject areas

  • General

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