ATPS-99: INTRATUMORAL INJECTION OF AN IN VITRO SYNTHESIZED EFEMP1-DERIVED TUMOR SUPPRESSIVE PROTEIN PRODUCT, ZR30, INTO U251 INTRACRANIAL XENOGRAFTS DEMONSTRATES THERAPEUTIC POTENTIAL IN BRAIN CANCER

BACKGROUND: Therapeutics that could be successful in treating glioblastoma multiforme (GBM) must have multiple tumor suppressive effects targeting the growth and invasion of different tumor cell subpopulations as well as tumor-associated vascularization. Dissection and characterization of functional domains in the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) identified an EFEMP1 variant named as "EFEMP1-derived tumor suppression protein" (ETSP), which suppressed the growth of both high-EGFR tumor mass forming cell and low EGFR stem-like tumor initiating cell subpopulations of U251. ZR30 is an in vitro synthesized protein product based on the sequence of ETSP with removal of the signal peptide, for use as cancer therapeutic via intratumoral injection. METHODS: Thirty-six mice of similar weight and physical condition, 1 week post-intracranial implantation of U251 (1X105 cells) were randomized into four groups, injected with 5 or 10 µl (350 or 700 ng ZR30) or the same volumes of saline, into the site of the cell implantation, at 10 and 21 days post cell implantation, respectively. RESULTS: Significant improvement in survival of mice treated with ZR30 in comparison with saline given at both time points was observed. CONCLUSIONS: The overall findings from the first in vivo efficacy test support the potential for success in treating brain cancer by applying ZR30 into the resection cavity at the time of completing partial or total tumor removal, and/or continuing to apply it to the surrounding tissue via convection enhanced delivery.