Targeted tumor cell death induced by autologous tumor-specific T lymphocyte recognition of wild-type p53-derived peptides.
Autologous tumor-specific T lymphocyte (ATTL) lines were derived from the peripheral blood mononuclear cells (PBMC) of a healthy volunteer with human leukocyte antigen (HLA) -A*0201. These lines were achieved using interleukins -1beta, -2, -4, and -6 and the p53-based peptide from the 264-272 sequence of the wild-type p53 protein with a strong affinity against HLA-A*0201.;The frequencies of CD3+, CD4+, and CD8+ lymphocytes were 94-96%, 30-34%, and 69-74%, respectively. ATTLs killed most of the T2 cells pulsed with p53-derived peptide, but not against the T2 cells non-pulsed or pulsed with an irrelevant peptide. ATTLs also killed TKB-14 cells, which have been derived from human glioblastoma multiforme, and exhibited HLA-A*0201 molecule and immunohistochemical accumulation of p53 protein. These cytotoxic activities were inhibited by anti-CD3, anti-CD8, and anti-class I antibodies. These findings suggested that these ATTL lines might include CTL populations, which could recognize p53-derived peptide on HLA-A*0201 and the p53-based peptide may play as an antigen on HLA-A*0201. When tumor antigens would be more analyzed in the future, ATTL could be induced without the primary-cultured cells from tumor tissue and could be applied for cancer therapy.
Tsurushima
Hideo
H
Faculty of Medicine, Department of Neuro Surgery, University of the Ryukyus, Okinawa, Japan. hideo-tsurushima@aist.go.jp
Yoshii
Yoshihiko
Y
Leong
Kam W
KW
Ohno
Tadao
T
D000954:Antigens, Surface / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D020014:K562 Cells; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D000954:Antigens, Surface; D017252:CD3 Complex; D015234:HLA-A Antigens; D010455:Peptides; D016159:Tumor Suppressor Protein p53