E. Celis et al., INDUCTION OF ANTITUMOR CYTOTOXIC T-LYMPHOCYTES IN NORMAL HUMANS USINGPRIMARY CULTURES AND SYNTHETIC PEPTIDE EPITOPES, Proceedings of the National Academy of Sciences of the United Statesof America, 91(6), 1994, pp. 2105-2109
Cytotoxic T lymphocytes (CTLs) recognize peptide antigens associated w
ith cell surface major histocompatibility complex (MHC) molecules. The
identification of tumor cell-derived peptides capable of eliciting an
ti-tumor CTL responses would enable the design of antigen-specific imm
unotherapies. Our strategy to identify such potentially therapeutic pe
ptides 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 strat
egy, we have identified a nine-residue epitope, derived from the produ
ct of the tumor-associated gene MAGE-3, which has the capacity to indu
ce in vitro CTLs that kill melanoma and other tumor cell lines. These
results show the primary in vitro induction of tumor-specific human CT
Ls and illustrate the feasibility of ex vivo antigen-specific approach
es to the immunological therapy of cancer.