Antitumor effects of murine bone marrow-derived dendritic cells infected with xenogeneic livin alpha recombinant adenoviral vectors against Lewis lung carcinoma.
Transduction with recombinant, replication-defective adenoviral (rAd) vectors encoding a transgene is an efficient method for gene transfer into dendritic cells (DCs). Livin is a member of the inhibitor of apoptosis protein family. Lung cancer and many other tumors express livin at high levels; whereas, normal fully differentiated cells generally do not. Therefore, livin represents a tumor-specific target for cancer vaccine therapy. Self proteins like livin may not stimulate potent antitumor immune responses due to central immunologic tolerance. Small variations in protein sequence that may exist between homologous proteins of different species can break tolerance to the native antigen. To study immunogenicity of a xenogeneic livin protein, we constructed an recombinant adenoviral vectors containing the human livin alpha genes (rAd-hlivin alpha) and vaccinated C57BL/6 mice with mouse bone marrow dendritic cells (BMDCs) transfected with rAd-hlivin alpha gave rise to potent livin-specific cytotoxic T lymphocyte (CTL) capable of lysing Lewis lung carcinoma (LLC) cells. Moreover, vaccination of mice with rAd-hlivin alpha-transduced DCs (rAd-hlivin alpha DCs) induced a potent protective and therapeutic anti-tumor immunity to LLC in a subcutaneous model along with prolonged survival compared to mice vaccinated with control recombinant adenovirus-transduced DCs(rAd-c DCs) or DCs alone. Therefore, xenogeneic differences between human and murine sequences might be exploited to develop immunogenic tumor vaccines.
Xie
Junping
J
Department of Respiratory Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiong
Liang
L
Tao
Xiaonan
X
Li
Xiao
X
Su
Yuan
Y
Hou
Xiaohua
X
Shi
Huanzhong
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D019496:Cancer Vaccines; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins