Enhanced induction of anti-tumor immunity in human and mouse by dendritic cells pulsed with recombinant TAT fused human survivin protein.
Survivin (SVV), a member of the inhibitors of apoptosis, has been considered as an ideal tumor-associated antigen due to its broad expression pattern in many types of human malignancies. Here, SVV-specific immune responses were evaluated with dendritic cells (DCs) loaded with a recombinant tatPTD fused SVV (tatSVV) protein both in vitro and in vivo system. The tatPTD fusion allowed for highly efficient and reproducible protein delivery into the DCs even in the presence of a phagocytosis inhibitor. The level of SVV-specific cytotoxic T-cell response appeared to be significantly higher for the T-cell line that was primed with the tatSVV-pulsed DCs, as compared to the T-cell line produced with naked (n)-SVV-pulsed DCs in vitro. Mice that received a xenogeneic tatSVV-pulsed DC vaccine developed a higher immune response than mice vaccinated with the nSVV-pulsed DCs and exhibited prolonged mean survival rate, though mice injected with the DCs alone or the nSVV-pulsed DC also showed anti-tumor effects in the subcutaneous GL26 glioma model. These results suggest that vaccination with DCs pulsed with tatSVV is an effective way for the SVV-targeting cancer vaccine to induce an effective anti-tumor responses.
Cho
Hyun-Il
HI
Department of Microbiology, College of Medicine, Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, South Korea.
Kim
Eun-Kyung
EK
Park
Soo-Young
SY
Lee
Su Kyung
SK
Hong
Yong-Kil
YK
Kim
Tai-Gyu
TG
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016019:Survival Analysis; D000077022:Survivin; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma