[Experimental study on activating antileukemic T cells by vaccination with dendritic cells pulsed with survivin].
The objective of this study is to investigate the effect of vaccination with dendritic cells pulsed with survivin antigen on activation of antileukemic T cells, and inhibiting proliferation of leukemic cells. The expression of survivin on acute leukemic cells were detected by cofocal microscopy and immunoprecipitation-Western blot. DCs collected from peripheral blood mononuclear cells were pulsed with survivin purified proteins. Stimulation index (SI) and antileukemia CTL induction were analyzed with (3)H-TdR incorporation and (51)Cr releasing assay, respectively. The phenotype of T cells and DCs were identified by flow cytometry. By immunofluorescence of bone marrow and peripheral blood mononuclear cells, survivin expression was detected in 16 out of 19 AML cases (84.2%). The results showed that survivin fluorescence distribution was in cytoplasm. DCs from peripheral blood mononuclear cells were successfully induced, with typical DC morphologic characteristic. The vaccination with dendritic cells pulsed with survivin antigen dramatically stimulated the proliferation of T cells. The DCs loading survivin activated T cells with higher CD4(+) T(H) ratio as compared with DCs group, T cells activated with DCs expressed CD8 and CD56. Survivin DCs significantly inhibited the growth of leukemic cells in vitro. In conclusion, survivin antigen expressed in the cytoplasm of leukemic cells, leukemic vaccination with DCs pulsed with survivin antigen in vitro inhibited the proliferation of leukemic cells, that may be a pathway for therapy of leukemia.
Zhang
Xiao-Hui
XH
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. zhangxh100@sina.com
Xia
Ling-Hui
LH
Liu
Zhong-Ping
ZP
Wei
Wen-Ning
WN
Hu
Yu
Y
Song
Shan-Jun
SJ
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D005434:Flow Cytometry; D018922:HL-60 Cells; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016219:Immunotherapy, Adoptive; D051034:Inhibitor of Apoptosis Proteins; D020014:K562 Cells; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000276:immunology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D009363:Neoplasm Proteins; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods
D015703:Antigens, CD; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D006684:HLA-DR Antigens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin