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Induction of antitumor cytotoxic T lymphocytes with a MAGE-3-encoded synthetic peptide presented by human leukocytes antigen-A24.

Abstract
For the development of immunotherapy using MAGE peptides, the identification of additional tumor antigens is required. Because HLA-A24 is the most common allele in Japanese and is also frequently present in Caucasians, MAGE-3-encoded synthetic peptides with binding affinity for HLA-A24 were thus tested for the induction of specific CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A24 healthy donors using a simplified method. By using a peptide with a sequence of IMPKAGLLI (amino acid position in MAGE-3 195-203), the CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and by also using interleukin 7 and keyhole limpet hemocyanin for a primary culture. The induced CTLs could lyse HLA-A24 carcinoma cells expressing MAGE-3, as well as the peptide-pulsed target cells, in an HLA class-I restricted manner. The identification of the MAGE-3/HLA-A24 peptide, IMPKAGLLI, may thus potentially offer the opportunities to design peptide-based immunotherapeutic approaches that might prove to be effective in treating patients with MAGE-3-positive malignant tumors.
AuthorsF Tanaka, T Fujie, K Tahara, M Mori, K Takesako, A Sette, E Celis, T Akiyoshi
JournalCancer research (Cancer Res) Vol. 57 Issue 20 Pg. 4465-8 (Oct 15 1997) ISSN: 0008-5472 [Print] United States
PMID9377553 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Neoplasm
  • HLA-A Antigens
  • HLA-A24 Antigen
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Oligopeptides
Topics
  • Alleles
  • Amino Acid Sequence
  • Antigens, Neoplasm (biosynthesis, immunology)
  • B-Lymphocytes
  • Binding Sites
  • Cell Line
  • Colonic Neoplasms
  • Cytotoxicity, Immunologic
  • Esophageal Neoplasms
  • HLA-A Antigens (immunology)
  • HLA-A24 Antigen
  • Humans
  • Immunotherapy (methods)
  • Japan
  • Leukemia
  • Neoplasm Proteins (biosynthesis, chemistry, immunology)
  • Oligopeptides (chemistry, immunology)
  • Polymerase Chain Reaction
  • Reference Values
  • Stomach Neoplasms
  • T-Lymphocytes, Cytotoxic (immunology)
  • Tumor Cells, Cultured
  • White People

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