Antitumor effects of murine bone marrow-derived dendritic cells infected with xenogeneic livin α recombinant adenoviral vectors against Lewis lung carcinoma

Abstract

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 α genes (rAd-hlivin α) and vaccinated C57BL/6 mice with mouse bone marrow dendritic cells (BMDCs) transfected with rAd-hlivin α 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 α-transduced DCs (rAd-hlivin α 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.