Cancer Stromal Targeting Therapy

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.