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Project

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

Funder: National Cancer Institute

Funding period
USD 300 K
Funding amount
Abstract
Project Summary/Abstract Bladder cancer causes over 165,000 annual deaths worldwide with 70,000 new cases and 16,000 deaths reported in the US. Treatment of superficial bladder cancer by resection and BCG administration is unsuccessful in 40% of cases with recurrences eventually requiring cystectomy or other aggressive therapy; new therapies are needed. The role of Epidermal Growth Factor Receptor (EGFR) in bladder cancer pathogenesis has been well established and its pathologic expression on the luminal side of uroepithelial cells in 70% of patients provides an ideal target for intravesical targeted therapy. We have previously demonstrated DTEGF?a single chain protein, encoding modified diphtheria toxin (DT) that 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 cancer, as well as in a number of xenograph explants of human bladder cancer in nude mice. Toxicity was not observed in these murine studies, nor in a pilot study in dogs demonstrated intravesical DTEGF was well tolerated at concentrations well above those needed for efficacy. IND-enabling studies are needed for DTEGF to move into the clinical testing. While we have preclinical proof-of-concept with DTEGF, another company has demonstrated Phase II clinical proof-of-concept with an EpCAM-toxinA fusion- toxin demonstrating 40% complete response in superficial bladder cancer patients. Their work provides a proven developmental path for our EGFR targeted toxin. The present grant application proposes to optimize intravesical administration and subsequently complete IND-enabling safety studies, hold a pre-IND meeting and complete an IND application. Completion of this work would position our agent as one with a very high likelihood success to be ready for clinically testing. We anticipate DTEGF to address the unmet need of patients that fail BCG (40%) and over express EGFR (70%) and eventually become a first line therapy that will likely work with EpCAM-targeted and other therapies to benefit the majority of patients.
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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Biotechnology

  • RCDC

    Cancer

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Clinical Medicine and Science