Generation of specific anti-melanoma reactivity by stimulation of human tumor-infiltrating lymphocytes with MAGE-1 synthetic peptide

Cancer Immunol Immunother. 1994 Aug;39(2):105-16. doi: 10.1007/BF01525316.


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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / pharmacology*
  • B-Lymphocytes / immunology
  • Base Sequence
  • Cell Division / physiology
  • Cell Transformation, Viral
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Epitopes
  • Gene Expression
  • HLA-A1 Antigen
  • Herpesvirus 4, Human
  • Humans
  • Immunotherapy, Adoptive
  • Interleukin-2 / pharmacology
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocytes, Tumor-Infiltrating / cytology*
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / blood
  • Melanoma / genetics
  • Melanoma / immunology*
  • Melanoma-Specific Antigens
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • RNA, Neoplasm / analysis
  • Sensitivity and Specificity
  • Stimulation, Chemical
  • T-Lymphocytes, Cytotoxic / cytology*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology


  • Antigens, Neoplasm
  • Cytokines
  • Epitopes
  • HLA-A1 Antigen
  • Interleukin-2
  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Interleukin-4