DT-EGF Toxic Fusion Protein for the Treatment of Bladder Cancer

Project Summary Abstract Bladder cancer causes overannual deaths worldwide withnew cases anddeaths reported in the USTreatment of superficial bladder cancer by resection and BCG administration is unsuccessful inof cases with recurrences eventually requiring cystectomy or other aggressive therapynew therapies are neededThe role of Epidermal Growth Factor ReceptorEGFRin bladder cancer pathogenesis has been well established and its pathologic expression on the luminal side of uroepithelial cells inof patients provides an ideal target for intravesical targeted therapyWe have previously demonstrated DTEGF a single chain proteinencoding modified diphtheria toxinDTthat has replaced the B chain sequence normally enabling cell entry with that of Epidermal Growth Factor was efficacious in a syngeneic rodent model of bladder canceras well as in a number of xenograph explants of human bladder cancer in nude miceToxicity was not observed in these murine studiesnor in a pilot study in dogs demonstrated intravesical DTEGF was well tolerated at concentrations well above those needed for efficacyIND enabling studies are needed for DTEGF to move into the clinical testingWhile we have preclinical proof of concept with DTEGFanother company has demonstrated Phase II clinical proof of concept with an EpCAM toxinA fusiontoxin demonstratingcomplete response in superficial bladder cancer patientsTheir work provides a proven developmental path for our EGFR targeted toxinThe present grant application proposes to optimize intravesical administration and subsequently complete IND enabling safety studieshold a pre IND meeting and complete an IND applicationCompletion of this work would position our agent as one with a very high likelihood success to be ready for clinically testingWe anticipate DTEGF to address the unmet need of patients that fail BCGand over express EGFRand eventually become a first line therapy that will likely work with EpCAM targeted and other therapies to benefit the majority of patients Project Narrative Annually in the USnew cases anddeaths are due to bladder cancerThis project will complete the work needed for a new therapy that targets the Epidermal Growth Factor Receptor present on bladder cancer cells to be ready for testing in bladder cancer patients