Induction of anti-tumor cytotoxic T lymphocytes in normal humans using primary cultures and synthetic peptide epitopes.
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.
Celis
E
E
Cytel, San Diego, CA 92121.
Tsai
V
V
Crimi
C
C
DeMars
R
R
Wentworth
P A
PA
Chesnut
R W
RW
Grey
H M
HM
Sette
A
A
Serra
H M
HM
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology*; D015788:HLA-A1 Antigen / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000939:Epitopes; D015788:HLA-A1 Antigen; C072013:MAGEA3 protein, human; C072012:MAGEB2 protein, human; D009363:Neoplasm Proteins; D010455:Peptides