Effective antitumor immunity against murine gliomas using dendritic             cells transduced with hTERTC27 recombinant adenovirus.
hTERTC27, a 27-kDa hTERT C-terminal polypeptide has been demonstrated to cause hTERT-positive HeLa cell apoptosis and inhibits the growth of mouse melanoma. hTERTC27 has been associated with telomere dysfunction, regulation of gene-regulated apoptosis, the cell cycle and activation of natural killer (NK) cells, but its mechanism of action is not fully understood. Here, we report that dendritic cells (DCs) transduced with hTERTC27 can increase T-cell proliferation, and augment the concentration of interleukin-2 (IL-2) and interferon-γ (IFN-γ) in the supernatants of T cells. It can also induce antigen-specific cytotoxic T lymphocytes (CTL) against glioma cells in vitro. Moreover, hTERTC27 gene-transduced DCs exhibit a very potent cytotoxicity to glioma cells in vivo. It could prolong the survival time and inhibit the growth of glioma-bearing mice. These data suggest that hTERTC27 gene-transduced DCs can efficiently enhance immunity against gliomas in vitro and in vivo.
Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China.
Han-Xian
HX
Gong
Lei
L
He
Xiang-Pen
XP
Li
Yi-Dong
YD
Wang
Yi
Y
Li
Jun-Jian
JJ
Huang
Ziling
Z
Wang
Dan
D
Xie
Hsiang-Fu
HF
Kung
Ying
Y
Peng
D056704:Adaptive Immunity; D000256:Adenoviridae / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000637:transplantation*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014161:Transduction, Genetic; D047368:Tumor Burden
D007376:Interleukin-2; D010446:Peptide Fragments; D007371:Interferon-gamma; C509186:TERT protein, human; D019098:Telomerase