Antibody Conjugate Therapeutics: Challenges and Potential
Antibody Conjugate Therapeutics: Challenges and Potential
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DOI：
10.1158/1078-0432.ccr-11-1417
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发表时间：
2011-10-15
影响因子：
11.5
通讯作者：
Chari, Ravi V. J.
中科院分区：
文献类型：
--
作者：
Teicher, Beverly A.;Chari, Ravi V. J.
抗体偶联物是一类不同的治疗药物，由与针对肿瘤细胞表达的特定细胞表面靶点的抗体或抗体片段共价连接的细胞毒性剂组成。针对恶性细胞表面靶点的抗体可用于药物递送的概念并不新鲜。抗体偶联物的历史以已被识别和克服的障碍为标志。早期的缀合物使用小鼠抗体;具有免疫原性（蛋白质）、毒性太大或效力不够的细胞毒性剂;以及在循环中不够稳定的接头。研究人员已经探索了使用抗体将细胞毒性剂靶向恶性细胞的4种主要途径：抗体-蛋白质毒素（或抗体片段-蛋白质毒素融合物）缀合物、抗体-螯合的放射性核素缀合物、抗体-小分子药物缀合物和抗体-酶缀合物，所述抗体-酶缀合物与小分子前药一起沿着施用，所述小分子前药需要通过缀合的酶代谢以释放活化的物质。只有抗体-放射性核素偶联物和抗体-药物偶联物达到了监管审批阶段，目前有近20种抗体偶联物处于临床试验阶段。这项技术成为改善癌症患者治疗的主要贡献者的时机可能已经到来。临床癌症研究; 17（20）; 6389-97。(C)2011年AACR。
Antibody conjugates are a diverse class of therapeutics consisting of a cytotoxic agent linked covalently to an antibody or antibody fragment directed toward a specific cell surface target expressed by tumor cells. The notion that antibodies directed toward targets on the surface of malignant cells could be used for drug delivery is not new. The history of antibody conjugates is marked by hurdles that have been identified and overcome. Early conjugates used mouse antibodies; cytotoxic agents that were immunogenic (proteins), too toxic, or not sufficiently potent; and linkers that were not sufficiently stable in circulation. Investigators have explored 4 main avenues using antibodies to target cytotoxic agents to malignant cells: antibody-protein toxin (or antibody fragment-protein toxin fusion) conjugates, antibody-chelated radionuclide conjugates, antibody-small-molecule drug conjugates, and antibody-enzyme conjugates administered along with small-molecule prodrugs that require metabolism by the conjugated enzyme to release the activated species. Only antibody-radionuclide conjugates and antibody-drug conjugates have reached the regulatory approval stage, and nearly 20 antibody conjugates are currently in clinical trials. The time may have come for this technology to become a major contributor to improving treatment for cancer patients. Clin Cancer Res; 17(20); 6389-97. (C) 2011 AACR.