Generation of specific anti-melanoma reactivity by stimulation of human tumor-infiltrating lymphocytes with MAGE-1 synthetic peptide.
The MAGE-1 gene encodes a tumor-specific antigen, MZ2-E, which is recognized by cloned, specific cytolytic T cells (CTL) derived from the peripheral blood of a patient with melanoma. We have produced a MAGE-1-specific CTL line derived from the tumor-infiltrating lymphocytes (TIL) of a melanoma patient by weekly restimulation with autologous EBV-B cells pulsed with the synthetic HLA-A1-restricted MAGE-1 epitope nonapeptide EADPTGHSY. The 1277.A TIL line grew in long-term culture in low-dose interleukin-2 (IL-2) and IL-4, and exhibited antigen-specific, MHC-class-I-restricted lysis of HLA-A1-bearing MAGE-1+ cell lines. Cytolysis of target cells pulsed with the synthetic MAGE-1 decapeptide KEADPTGHSY was superior to that of cells pulsed with the immunodominant nonapeptide. Single amino-acid or even side-chain substitutions in the immunodominant nonamer abrogated cytolysis. 1277.A TIL specifically secreted tumor necrosis factor alpha after co-incubation with HLA-A1-expressing MAGE-1+ cell lines or fresh tumor. These data suggest that tumor-antigen-specific, MHC-restricted CTL may be grown from TIL in the presence of synthetic epitope peptides and expanded for adoptive immunotherapy in melanoma patients.
Salgaller
M L
ML
Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892.
Weber
J S
JS
Koenig
S
S
Yannelli
J R
JR
Rosenberg
S A
SA
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002472:Cell Transformation, Viral; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D015870:Gene Expression; D015788:HLA-A1 Antigen; D004854:Herpesvirus 4, Human; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D008545:Melanoma / Q000097:blood / Q000235:genetics / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm / Q000032:analysis; D012680:Sensitivity and Specificity; D013268:Stimulation, Chemical; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D000951:Antigens, Neoplasm; D016207:Cytokines; D000939:Epitopes; D015788:HLA-A1 Antigen; D007376:Interleukin-2; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D015847:Interleukin-4