细胞工程制药.解读.ppt

+ - Sialidase ? ? ? ? ? ? 2001.Konenbreg, The generation and presentation of glycolipid for CD1d ?-GalCer Gal ?1,6GalCer + CD1d-coated plate + + APC + + ?-Gal A-/- APC + Gal ?1,2GalCer +NKT hybridomas - ?-Gal A (lysosomal glycosidase~ Gal ?1,2/ ?1,4) 2004.Bendelac, Lipid transfer protein (LTP) Hypothesis: Lysosome is a most important compartment for efficient CD1d antigen presentation that provides glycosidases and lipid transfer proteins NKT cell antigen presentation pathway is that glycolipids are endocytosized and processed with glycosidases in lysosome. The presentation of the disaccharide glycosylceramide is a tightly and precisely regulated process that involves lipid transfer proteins and glycosidases, thus they might have complete different therapeutic effect. Lysosomal Glycosidases ? Beta-glucosidase Alpha-galactosidase Beta-galactosidase Alpha-fucosidase Alpha-mannosidase Beta-mannosidase Beta-glucoronidase Alpha-N-acetylgalactosaminidase Beta-N-acetylglucosaminidase GalNAc-6-sulfate sulfatase Lysosomal carboxypeptidase Cathepsin Hexosaminidase A/B 32 An exciting discovery of NKT cell natural ligand Hexosaminidase A/B remove beta-linked GalNAc residues found on glycosphingolipids the natural products of it were screened as ligands for NKT cells isoglobotrihexosylceramide (iGb3) 33 Synthesis of ?-glucosylceramide based disaccharide glycosylceramide (budget year 1-2) Testing the uptake and processing by APCs (Budget year 2-3 ) Testing anti-tumpr activity (Budget year 2-3 ) Finding the best candidates in cancer treatment Summarize the best candidates? uptake and processing by in APCs Finding the most optimal the link between NKT cell activation and anti-tumor immunity (Budget year 4) 34 一、实验室设置 细胞工程实验室它必须满足三个基本的需要，即： 细胞工程制药专题二 第一节 细胞工程实验室技术 2、辅助实验室 细胞学实验室对培养材料进行细胞学鉴定和研究。 要求清洁、明亮、干燥，使各种光学仪器不受潮湿 和灰尘污染。 摄影室及暗室进行培养材料的摄影记录和暗室显影， 有条件可建立。 生化分析室以培养细胞产物为主要目的的实验室中， 应建立相应的分析化验实验室，以便对培养物的有 效成