Ad-6Ckine/IFNγ Fusion Gene-modified Dendritic Cells Act As An Adjuvant To Induce Anti-hepatic Cancer And Anti-colonal Cancer Immunity

Backbround: Many tumors express tumor-associated antigens (TAA). Antigen presenting cells (APC), such as dendritic cells (DC) process and present TAAs to T cells, thereby eliciting a tumor-specific immune response. However, because TAAs are considered autologous, many tumor cells often escape antitumor immunosurveillance. In addition, various factors affecting immune escape include limited expression of major histocompatibility complex (MHC) antigens and costimulatory molecules, the production of immune inhibitory cytokines and tumorigenic viruses that inhibit the development of DC. Therefore, recruitment of professional APC to the tumor site, up-regulating the expression of the MHC and associated costimulatory molecules, and enhancing the T cell-primed capability of APC may be essential for generating specific anti-tumor immune responses. Dendritic cells are the most functional of the professional APC, with a unique ability to capture and process antigens in the peripheral blood and tissues. DC then migrate to draining lymphoid organs, where they select rare antigen-specific T cells in which to initiate the immune responses. Dendritic cells also present antigens to CD4+ T-helper cells, which in turn regulate the antigen-specific CD8+ cytotoxic T cells and B cells, as well as non-antigen-specific macrophages, eosinophils and natural killer (NK) cells.The ability of DC to capture, process and present antigens to lymphocytes, and to induce and sustain primary immune responses makes them optimal candidates for vaccination protocols in cancer. Advancements in the isolation and propagation of DC in vitro include the use of DC as adjuvants to stimulate antigen-specific T cell activation and anticancer immunity. In immunotherapeutics, DC are pulsed with (a) defined peptides of known sequences, (b) undefined acid-eluted peptides from autologous tumors, (c) apoptotic tumor cells, (d) whole tumor lysates, (e) retroviral and adenoviral vectors, (f) tumor cell-derived RNA, (g) fusion of DC with tumor cells, and (h) exosomes derived from DC...