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Abstract
Grant Number: 1R43CA102806-01 PI Name: LUXEMBOURG, ALAIN T. PI Email: aluxembourg@ichorms.com PI Title: SENIOR RESEARCH SCIENTIST Project Title: Cytokine Gene Transfer for Metastatic Colorectal Cancer Abstract: DESCRIPTION (provided by applicant): Metastatic colon cancer represents a significant healthcare problem in the U.S., with 50,000 new cases diagnosed annually and median survival at less than 2 years. The identification of tumor-associated antigens in colon cancer provides the basis to evaluate immunological treatment strategies. Despite showing promise in some cancers, immunotherapy using systemic cytokine administration has largely disappointed due to low response rates and high toxicity. Intratumoral gene transfer has been proposed as an alternative means of administration to improve the therapeutic and toxicologic profile of these molecules. Unfortunately, clinical implementation is hampered by the lack of clinically viable gene delivery vectors. Recent studies of in vivo electroporation demonstrate dramatic improvement in intratumoral delivery of therapeutic agents. Ichor has developed proprietary electroporation technology enabling safe and effective application of the procedure. Initial preclinical work suggests that Ichor's system is a promising means for intratumoral cytokine gene delivery. Under FLAIR Phase-l, Ichor will evaluate its electroporation technology for delivery of cytokine genes into hepatic colon cancer metastases. Research will include rodent studies designed to establish effective treatment protocols. Successful completion will lead to formal toxicology studies and subsequent clinical investigation of the procedure in patients with unresectable colorectal metastases, conducted under FLAIR Phase-lI.
Thesaurus Terms:
colorectal neoplasm, cytokine, electroporation, gene delivery system, gene therapy, method development
disease /disorder model, gene expression, gene frequency, interferon alpha, interleukin 12, liver neoplasm, metastasis, neoplasm /cancer immunology, plasmid, therapy adverse effect
biotechnology, laboratory mouse, laboratory rat, polymerase chain reaction, transfection /expression vector
Institution: ICHOR MEDICAL SYSTEMS 6310 NANCY RIDGE DR, STE 107 SAN DIEGO, CA 92121 Fiscal Year: 2003 Department: Project Start: 10-JUL-2003 Project End: 30-JUN-2005 ICD: NATIONAL CANCER INSTITUTE IRG: ZCA1