抗体靶向治疗药物 ppt课件培训讲学.pptVIP

抗体靶向治疗药物 ;;Mechanism of Action: Monoclonal Ab;Graphic representation of progression of monoclonal antibodies from murine to chimeric to humanized to PRIMATIZED? and human. The more human the antibody is, the less likely it will generate an immune response and the more utility it has for chronic (repeat) therapy.;与单抗偶联的常用“弹头”药物;Physical characteristics of some therapeutic radionuclides;Monoclonal antibodies in the order of FDA-approval;US and EU therapeutic mAb approvals to date;1, chimeric mAbs, all products (n = 39); 2, oncological chimeric mAbs (n = 21); 3, immunological chimeric mAbs (n = 9); 4, chimeric mAbs, 1987–1997 (n = 20); 5, humanized mAbs, all products (n = 102); 6, oncological humanized mAbs (n = 46); 7, immunological humanized mAbs (n = 34); 8, humanized mAbs, 1988–1997 (n = 46). ;Approval success rates for mAbs;影响抗体治疗的主要障碍 1. 异源抗体的免疫原性 (Immunogenicity of xenogeneic antibodies) 2. 抗原脱落进入血循环 (Shedding of antigen into circulation) 3. 肿瘤内血管的失调 (Disordered vasculature in tumors) 4. 肿瘤内静水压的增加 (Increased hydrostatic pressure in tumors) 5. 肿瘤表面抗原的异质性 (Heterogeneity of antigen on tumor surface) 6. 肿瘤效应细胞数量的限制 (Limited numbers of effector cells at tumor) 7. 免疫抑制性肿瘤微环境 (Immunosuppressive tumor microenvironment);Serial microPET imaging of 124I-labeled anti-CEA scFv-Fc fragments Parental human γ1 and H310A/H435Q double mutant in LS174T xenograft-bearing mice. The image marked scFv-Fc SM is a H310A single mutant of the mAb; scFv-Fc DM is a H310A/H435Q double mutant. ;Biodistribution of different mAb formats in two xenograft models; Camelid VhH-Ig and shark Ig-NARs are unusual immunoglobulin-like structures comprising a homodimeric pair of two chains of V-like and C-like domains (neither has a light chain), in which the displayed V domains bind target independently. Shark Ig-NARs comprise a homodimer of one variable domain (V-NAR) and five