A MAGE-1-encoded HLA-A24-binding synthetic peptide induces specific anti-tumor cytotoxic T lymphocytes

Int J Cancer. 1999 Jan 18;80(2):169-72. doi: 10.1002/(sici)1097-0215(19990118)80:2<169::aid-ijc1>3.0.co;2-p.

Abstract

Although several MAGE-1 peptides have already been identified, the MAGE-1-encoded peptide presented by HLA-A24, which is the most common allele in Japanese population and is also frequently present in Caucasians, might have a wide applicability for immunotherapy using these peptides. To identify this potential peptide, we examined the induction of specific cytotoxic T lymphocytes (CTL) from the peripheral-blood mononuclear cells (PBMC) in HLA-A24 healthy donors by in vitro stimulation with MAGE-1-encoded synthetic peptides with a binding affinity for HLA-A24, by a simplified method. Of the 5 peptides tested, the highest HLA binder (NYKHCFPEI) was able to elicit CTL from unseparated PBMC by stimulation with freshly isolated, peptide-pulsed PMBC as antigen-presenting cells (APC) and by also using interleukin 7 and keyhole-limpet hemocyanin for a primary culture. The induced CTL could thus lyse HLA-A24 tumor cells expressing MAGE-1, as well as the peptide-pulsed target cells, in an HLA-class-I-restricted manner. By using the MAGE-1/HLA-A24 peptide, NYKHCFPEI, we found it possible to immunize many more patients, especially Japanese patients, by means of such peptide-based immunotherapeutic approaches to MAGE-1-positive malignant tumors.

MeSH terms

  • Alleles
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Antigens, Neoplasm
  • Cell Line
  • Genetic Code
  • HLA-A Antigens / genetics*
  • HLA-A Antigens / immunology
  • Humans
  • Melanoma-Specific Antigens
  • Neoplasm Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • HLA-A Antigens
  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • RNA, Messenger