免疫检测 预防和治疗.ppt

Immunotherapy against Cancer -vaccination GVAX (GMCSF gone modified tumor vaccine，瘤苗) Glenn Dranoff HMS DFCI 自体肿瘤细胞经过基因修饰表达后，体外灭活进行皮下接种 James P. AllisonHHMI MSKC Immunotherapy against Cancer ----blocking of CTLA-4 + GVAX Blocking antibody against CTLA-4 Anti-CTLA4 Immunotherapy against Cancer ----DC vaccination + lysis Acid elution synthesis extraction mRNA Antigen peptide Native peptide Cell lysate Tumor cell --Adoptive immunotherapy TILs 3. BRMs （biological response modifiers） and Immunosuppressors Type of BRM Examples Major Effect Bacteria Products BCG (卡介苗), C. Parvum (短小棒状杆菌)， muramyl dipepite (胞壁酰二肽)， trehalose dimycolate (海藻糖二霉菌酸酯) Activate macrophage， and NK cells Synthetic molecules Pyran copolymer (吡喃共聚物), MVE, poly I:C, pyrimidines(嘧啶) Induce IFN production Hormones Thymosin (胸腺素), thymulin(胸腺肽), thymopoietin(促胸腺生成素) Modulate T cell function 3. BRMs and Immunosuppressors Immunosuppressors Category Example Function Usage Folate (叶酸) antagonists Methotrexate (甲氨蝶呤) inhibits folate-depedent pathway (necessary for DNA synthesis) RA (70% clinical response), other autoimmune diseases Purine analogs (嘌呤类似物) 6-mercaptopurine (6-MP), (巯基嘌呤) Azathioprine(咪唑巯嘌呤) , fludarabine (氟达拉滨，STAT-1 inhibitor) , cladribine(克拉屈滨) Inhibits DNA synthesis Renal allograft rejection, RA, lymphoproliferative diseases, leukemia Alkylating (烷基化物) Agents Cyclophosphamide(环磷酰胺) Toxic for proliferating cells Vasculitides (血管炎) 3. BRMs and Immunosuppressors Immunosuppressors Category Example Function Usage Mycophenolate mofetil (次黄嘌呤核苷磷酸脱氢酶抑制剂) Blocking synthesis of purines Rejection after organ transplatation Leflunomide (来氟米特) Synthesis of pyrimidines RA, effect comparable to Methotrexate(甲氨蝶呤) Cyclosporine(环孢霉素), FK-506 (他克莫司) Block IL2 production Rejection after organ transplatation Rapmycin(雷帕霉素) Block cell proliferation Rejection after organ transplatation Immunoprevention Edward Jenner (牛痘疫苗防治天花) Portrait by John Raphael Smith. Reproduced courtesy of Yale U