Development of drug or gene delivery system for clinical application.

聚合物胶束有望利用EPR效应增加药物在肿瘤组织中的蓄积，并以较高的稳定性将各种药物纳入内核。胶束的大小可以控制在20 ~ 100nm的直径范围内，保证胶束不穿过正常的血管壁；因此，可以预期药物不良反应的发生率会降低。在临床前评价后，有几种抗癌剂结合胶束载体系统正在进行临床评价。其次，我们利用一种特殊的单克隆抗体（mAb）开发了一种新的针对肿瘤基质的细胞毒性免疫偶联物。这些新开发的免疫偶联物选择性地从泄漏的肿瘤血管外渗，结合到包膜肿瘤血管的肿瘤基质成分上，形成一个支架，从这个支架上有效地持续释放一种时间依赖性的抗癌药物。这种释放的抗癌剂随后扩散到整个肿瘤组织，导致肿瘤生长明显停止。肿瘤基质靶向治疗（CAST）是一种高效的肿瘤治疗新方式，利用细胞毒性药物与单克隆抗体结合，靶向肿瘤基质的特定惰性成分。

Polymeric micelles are expected to increase the accumulation of drugs in tumor tissues utilizing the EPR effect and to incorporate various kinds of drugs into the inner core with relatively high stability. The size of the micelles can be controlled within the diameter range of 20 to 100nm, to ensure that the micelles do not pass through normal vessel walls ; therefore, a reduced incidence of the adverse effects of the drugs may be expected. There are several anticancer agent-incorporated micelle carrier systems under clinical evaluation after our preclinical evaluation of them.Secondly, we developed a new cytotoxic immunoconjugates using a specially raised monoclonal antibody (mAb) to the tumor stroma. These newly developed immunoconjugates selectively extravasated from leaky tumor vessels, bound to the tumor stromal component ensleeving tumor vessels and created a scaffold, from which effective sustained release of a time-dependent anti-cancer agent occurred. This released anti-cancer agent subsequently diffused throughout the tumor tissue causing marked arrest of tumor growth. Cancer stromal targeting (CAST) therapy, utilizing a cytotoxic agent conjugated to a mAb directed at a specific inert constituent of the tumor stroma is thus validated as a highly effective new modality of oncological therapy.