Development of drug or gene delivery system for clinical application.

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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.