遗传工程抗体.pptVIP

基因工程抗体;Definition;第一代：多克隆抗血清 (polyclonal antibody) 第二代：细胞工程抗体——杂交瘤单克隆抗体(monoclnal antibody,McAb) 第三代：基因工程抗体 (genetic engineering antibody);单克隆抗体药物存在的一些问题：;应对策略;;一.鼠抗体人源化及人源抗体制备技术;嵌合抗体（chimeric antibody）: 在基因水平上将小鼠的Ig可变区与人的Ig恒定区嵌合在一起，所产生的抗体含有70-80% 的人的Ig分子的序列，在很大程度上减少了单克隆抗体的免疫原性，但这种抗体尚存20-30%的鼠源成分，在实际应用过程中仍可刺激机体产生较强的抗独特型反应。;Pr 鼠VH 人 CH Pr 鼠VL 人 CL;鼠VH;人 ︱鼠嵌合抗体;抗CD20抗体美罗华（IDEC-C2B8，Rituximab，Rituxan）;人改型抗体（CDR移植） ;CDR序列 ;二、改变抗体分子大小增强靶向性;（一）单链抗体的特性及应用;单链抗体的应用;;Computer-simulated model of xenoantibody/carbohydrate interaction in humans and non-human primates.?(A.)?Anti-carbohydrate single chain antibody (assession number IMFA) complexed with a trisaccharide carbohydrate antigen. Amino acids in key contact sites identified by crystallography are shown. The information can be accessed in the NCBI database by homology search for structural similarities.(B.)?The IGHV3-11 xenoantibody (122B) induced in human patients mounting an active immune response following placement on a bioartificial liver.?(C.)?Computer-simulated model of the IGHV3-11 human single chain xenoantibody (122B) aligned with the VH4-59 germline progenitor (clone 5, Fig 1).?(D.)?The IGHV3-11 VH?gene [9] and DPK5 light chain genes (clone 17, Fig 2) encode a xenoantibody expressed at high levels post-transplantation with porcine hearts and following immunization with porcine hepatocytes in rhesus monkeys. Kearns-Jonker?et al.?BMC Immunology?2007?8:3 ? doi:10.1186/1471-2172-8-3;（二）双特异性抗体的特点及应用;A BiTE (Bi-specific T Cell Engager) antibody ;双特异性抗体的应用 ;三、增强抗体效应功能