Matsumura Yasuhiro
Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center National Cancer Center.
Yakugaku Zasshi. 2017;137(5):529-534. doi: 10.1248/yakushi.16-00255-2.
Recent advances in antibody-drug conjugate (ADC) technology have shown considerable promise in targeted cancer therapy. The ADC strategy should be confined to highly toxic anticancer agents and not to ordinary anti-cancer agents (ACAs) because the affinity of monoclonal antibodies (mAbs) diminishes if more than three ACA molecules are conjugated. According to this principle, higher amounts of ADC should be administered so that each of the ACAs is conjugated to the mAbs. Therefore for an ordinary ACA, nanoparticles should be the preferred drug delivery system (DDS). A large body of clinical evidence indicates that abnormal coagulation occurs in a variety of cancer patients, especially in invasive cancers. Tissue factor (TF), expressed on the surface of various cancer cells and tumor vascular endothelial cells, is the trigger protein of extrinsic coagulation resulting in insoluble fibrin formation. We have developed mAbs against TF and human fibrin that reacted only with human fibrin and not with human fibrinogen. We now propose cancer stromal targeting (CAST) therapy and diagnosis, using a cytotoxic agent or radioisotope conjugated to a monoclonal Ab directed at a specific inert constituent of the tumor stroma, as a new modality especially for invasive cancer.
抗体药物偶联物（ADC）技术的最新进展在靶向癌症治疗中显示出了巨大的前景。ADC策略应局限于高毒性抗癌药物，而不是普通抗癌药物（ACA），因为如果偶联的ACA分子超过三个，单克隆抗体（mAb）的亲和力就会降低。根据这一原则，应给予更高剂量的ADC，以便每个ACA都能与mAb偶联。因此，对于普通ACA，纳米颗粒应该是首选的药物递送系统（DDS）。大量临床证据表明，各种癌症患者，尤其是浸润性癌症患者会出现异常凝血。组织因子（TF）表达于各种癌细胞和肿瘤血管内皮细胞表面，是外源性凝血的触发蛋白，可导致不溶性纤维蛋白形成。我们已经开发出了针对TF和人纤维蛋白的单克隆抗体，它们只与人纤维蛋白反应，而不与人纤维蛋白原反应。我们现在提出癌症基质靶向（CAST）治疗和诊断，即使用与针对肿瘤基质特定惰性成分的单克隆抗体偶联的细胞毒性药物或放射性同位素，作为一种新的治疗方式，尤其适用于浸润性癌症。
