Our laboratories have identified a receptor, urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180) which is expressed in several cancers [1-3]. Notably, uPARAP/Endo180-positive cancer cells include sarcomas and glioblastomas [4] (and our unpublished results). This receptor is responsible for collagen turnover during malignant cancer invasion. By conjugating potent anti-mitotic, synthetic N-alkylated isatin derivatives [5] to antibodies targeting this receptor forming immunoconjugates, we have recently shown that uPARAP/Endo180 can be utilized to deliver the toxin specifically to uPARAP/Endo180-positive cells in vitro. Using this strategy, we have found conditions where almost 100% of cells treated with an uPARAP/Endo180-targeted isatin-immunoconjugate were killed, while cells treated with non-targeted isatin-immunoconjugate were left fully viable. Our findings point to uPARAP/Endo180 as a potential target for anti-cancer therapy, and isatin derivatives as potential cytotoxic anti-cancer drugs in connection with targeted drug delivery. Current studies are focused on the development and optimization of several different approaches for the synthesis of isatin-immunoconjugates, delivery of other drugs including doxorubicin and small interfering (si)RNA, as well as investigating the structural and cellular requirements for successful drug delivery using these immunoconjugate systems. These studies may lead to the development of novel forms of targeted therapy against sarcomas and glioblastomas, for which there is a strong need for improved treatment.