Smith S
Curr Opin Mol Ther. 2001 Apr;3(2):198-203.
C242-DM1 is a tumor-activated immunotoxin under development by GlaxoSmithKline plc (formerly SmithKline Beecham plc), under licence from ImmunoGen Inc, as a potential treatment for colon tumor. It consists of a colon cancer-specific humanized antibody, C242, conjugated to the maytansine derivative DM1. In preclinical studies, C242-DM1 caused complete tumor regression in animal models of both human pancreatic and non-small cell lung cancer (NSCLC) at non-toxic doses. C242-DM1 has also been evaluated in an immunoconjugate combination with J-591 (Cornell University). The J591-DM1 immunoconjugate demonstrated effective, antigen-specific delivery of a highly cytotoxic drug to PSMA-positive Pca cells in vitro and in vivo with low systemic toxicity. Results from studies in monkeys showed that C242-DM1 had no significant toxicity or side effects, when administered at doses higher than those that were previously shown to completely eradicate human colon tumors in mice [271420]. ImmunoGen acquired the right to evaluate, and an option to license, technology related to maytansines from Takeda. In February 1999, ImmunoGen and SmithKline Beecham signed a US $45 million development and commercialization agreement for C242-DM1 [313493]. In August 1997, Immunogen received an SBIR grant to advance development of huC242-DM1 [258356]. EP-00425235, held by ImmunoGen, covers conjugated forms of ansamitocin (maytansine) derivatives. Takeda holds several patents for the production of ansamitocin and its analogs, the first one being JP-53124692.
C242-DM1是葛兰素史克公司（前身为史克必成公司）根据与ImmunoGen公司的许可协议正在研发的一种肿瘤激活免疫毒素，作为结肠癌的潜在治疗药物。它由一种结肠癌特异性人源化抗体C242与美登素衍生物DM1偶联而成。在临床前研究中，C242-DM1在无毒剂量下使人类胰腺癌和非小细胞肺癌（NSCLC）动物模型中的肿瘤完全消退。C242-DM1也已与J-591（康奈尔大学）联合进行免疫偶联物评估。J591-DM1免疫偶联物在体外和体内均显示出能将高细胞毒性药物有效、抗原特异性地递送至PSMA阳性前列腺癌细胞，且全身毒性较低。在猴子身上的研究结果表明，当以高于先前在小鼠中显示能完全根除人类结肠肿瘤的剂量给药时，C242-DM1没有明显的毒性或副作用[271420]。ImmunoGen从武田公司获得了评估与美登素相关技术的权利以及许可选择权。1999年2月，ImmunoGen与史克必成签署了一项价值4500万美元的C242-DM1开发和商业化协议[313493]。1997年8月，Immunogen获得了一项小企业创新研究（SBIR）资助，以推进huC242-DM1的开发[258356]。ImmunoGen持有的EP-00425235涵盖了安丝菌素（美登素）衍生物的偶联形式。武田公司拥有多项关于安丝菌素及其类似物生产的专利，第一项专利为JP-53124692。
