INDUCTION OF ANTITUMOR CYTOTOXIC T-LYMPHOCYTES IN NORMAL HUMANS USINGPRIMARY CULTURES AND SYNTHETIC PEPTIDE EPITOPES

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.