BIOTHERAPY OF BRAIN TUMORS BY RADIOIODINATED SAPC-DOPS NANOVESICLES

Molecular Targeting Technologies, Inc., West Chester PA

Investigators

Abstract

There is an urgent need for more effective drug delivery agents for treatment of brain tumors, which are among the most aggressive and intractable cancers. SapC-DOPS, a nanovesicle composed of saposin C (SapC) coupled to dioleoylphosphatidylserine (DOPS), has proven tumor targeting properties, which include crossing the blood-brain tumor barrier and binding the lipid tumor marker, extracellular phosphatidylserine (PS). It also exhibits antitumor activities in preclinical glioblastoma (GBM) models. We hypothesize that endowing SapC-DOPS nanovesicles with a radiolabeled lipophilic reporter will create a novel agent with superior efficacy for targeted radionuclide therapy (TRT) of GBMs. Treatment options for GBMs are very limited, and standard therapies with radiation and/or chemotherapy provide only modest survival benefits with potential deleterious effects. To address these issues, we propose to create a novel cancer-selective, targeted radiolabeled SapC-DOPS for TRT of GBMs. A unique advantage of MTTI's approach lies in the feedforward therapeutic mechanism of the novel compound: radiation exposure is known to increase PS externalization in tumor cells, thus leading to enhanced anticancer effects by PS-targeted SapC-DOPS nanovesicles. This proposal is backed by extensive, published and unpublished, preliminary data, the FDA Orphan Drug designation of SapC-DOPS, and an ongoing clinical phase I trial.