Project 3:
Development of Novel Targeted Therapeutics for Brain Tumor Treatment

Principal Investigator - John W. Park, MD
Clinical Co-Principal Investigator - Mitchel S. Berger, MD

High-grade gliomas remain a surgically incurable disease, largely because of infiltratative growth into surrounding normal brain. Radiotherapy and chemotherapy are limited by inadequate tumor specificity, inherent and/or acquired resistance, and the inability to achieve effective exposure within the brain without causing excessive systemic toxicity. Better therapies must achieve efficient delivery of agents not only to the brain but via selective and efficient targeting to the tumor cells themselves.

A research project of the UCSF Breast Cancer SPORE has resulted in development of an immunoliposome technology for receptor-targeted, intracellular drug delivery. This technology will now be applied to brain tumor treatment. Liposomes will be designed to contain a variety of toxic small molcules and nucleic acids. These liposomes will then be targeted to glioma cells by linkage to single-chain antibodies specific for tumor cells expressing EGFR or mutant EGFR. These immunoliposomes will then be targeted to the brain.

Following optimization and evaluation, the most promising constructs will be moved into clinical trials. This approach is expected to selectively increase drug delivery to brain tumors and to have a significant impact on the therapy of otherwise untreatable gliomas.