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Innovations in Biotechnology Part 7

Tham khảo tài liệu 'innovations in biotechnology part 7', kỹ thuật - công nghệ, cơ khí - chế tạo máy phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả | Translating 2A Research into Practice 171 satisfactory for short-term applications antibody intravenous infusion is not appropriate in many long-term treatments. Fang et al. 2007 describe a recombinant adeno-associated virus rAAV gene delivery system that allows regulated long-term expression of native fulllength mAbs in vivo. In this study a F2A sequence adjacent to a furin cleavage site AK RKRR was used to link the antibody heavy and light chain sequences. Notably the gene expression system included a rapamycin-regulated promoter that can be used to stop mAb production if treatment needs to be terminated. This system potentially offers patients a lifelong mAb therapy that requires only a single administration of an rAAV vector. Cytotoxic T-lymphocyte-associated antigen CTLA-4 also known as CD152 is a co-inhibitory molecule that functions to regulate T-cell activation. Antibodies that block the interaction of CTLA-4 with its ligands CD80 B7-1 and CD86 B7-2 can enhance immune responses including anti-tumour immunity for a brief review see Chambers et al. 2001 . Granulocyte-macrophage colony-stimulating factor GM-CSF is a bone marrow growth factor for APCs which has also been shown to enhance anti-tumour immune responses. Both preclinical animial models and early clinical development indicate synergy between GM-CSF tumour cell vaccination and CTLA-4 blockade Hurwitz et al. 2000 Hodi et al. 2003 Quezada et al. 2006 . To avoid anti-CTLA-4 side effects tumour cell lines expressing the full-length F2A anti-CTLA-4 mAb in addition to GM-CSF were administered locally at the immunization site Simmons et al. 2008 . Preliminary results suggest that the delivery of mAbs or proteins locally from immunotherapy cells should prove useful based on promising anti-tumour responses and the reduction of toxicity or adverse immune events associated with systemic exposure. 4.3.3 Cytokines and immunotherapy The cytokine Interleukin-12 IL-12 is a growth and maturation factor acting on both