Induction of antitumor cytotoxic T lymphocytes from the peripheral blood mononuclear cells of cancer patients using HLA-A2-restricted MAGE-3 peptide in vitro.
As the basis for the application of MAGE antigens to therapeutic use, the induction of peptide-specific CTLs has been investigated by the stimulation of peripheral blood mononuclear cells (PBMCs) with antigenic peptides derived from MAGE genes. However, the cross-reactivity of the peptide-induced CTLs to the target cells endogenously presenting the MAGE epitope, especially in cancer patients, remains controversial, despite the use of complicated manipulations. Because we recently developed a new simplified method to induce peptide-specific CTLs that killed MAGE expressing tumor cells from the PBMCs of a healthy donor, we examined the induction of specific CTLs by stimulation of PBMCs with HLA-A2-restricted MAGE-3 peptide in HLA-A2(+) cancer patients whose tumors expressed MAGE-3 by using the simple method. The CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells and by using interleukin 7 and keyhole limpet hemocyanin for the primary culture. All CTLs induced from the PBMCs of four cancer patients tested could thus lyse the HLA-A2 target cells pulsed with the peptide, and moreover, two of the CTLs were also able to kill HLA-A2 tumor cells expressing MAGE-3 in a HLA class I and A2-restricted manner. Therefore, these findings seem to indicate that HLA-A2-restricted MAGE-3 peptide may be potentially useful for specific immunotherapy in cancer patients.
Fujie
T
T
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu 874.
Tanaka
F
F
Mori
M
M
Takesako
K
K
Sugimachi
K
K
Akiyoshi
T
T
D000951:Antigens, Neoplasm / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000951:Antigens, Neoplasm; D016207:Cytokines; D015789:HLA-A2 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha