Modified E1A Constructs as a Novel Therapeutic Composition and Method for Stimulating the Immune System to Fight Cancer and Infectious Diseases
Tech ID: 02-09
Summary - The development of immunotherapeutic approaches to bolster tumor-specific responses is a major focus of immunology today. However, a major hurdle is the relatively low immunogenicity of tumor antigens. National Jewish Health researchers have developed and tested a novel therapeutic composition and method for stimulating the immune system to fight cancer and infectious diseases. They have defined the molecular basis for the high immunogenicity of E1A and have used this knowledge to develop a mutated form of E1A that is non-transforming and highly immunogenic (strong Th1 immune response is obtained). The mutated form of E1A can be used to enhance immunogenicity of any antigen by coexpressing the tumor antigen with the mutant form of E1A.
Potential Applications - Therapy for cervical cancers and melanomas (possibly other tumor types) Therapy for bacterial or viral infections such as HIV-1, hepatitis B and hepatitis C.
Advantages of Invention - The construct is non-transforming, immunogenic and anti-oncogenic. There are a number of different methods to coordinately express the mutant form of E1A and a tumor antigen, such as the construction of a chimeric gene coding for a fusionprotein consisting of E1A and the tumor antigen, a bicistronic vector that expresses E1A and a tumor antigen or recombinant adenovirus expressing E1A and a tumor antigen.
State of Development - National Jewish Health scientist has shown that: 1) expression of the mutated E1A inhibits baseline TGF-â production in tumor cells; and 2) expression of the mutated E1A inhibits production of TGF-â and reduces the expression of phosphatidylserine receptor (PSR) on tumor cells. 3) expression of the mutated E1A decreases HSP70 expression 4) In MCA tumor cells inefficiently induce E1A- specific cytotoxic T lymphocytes. 5) expression of a nucleic acid molecule encoding a mutated E1A protein-antigen chimera sensitized tumor cells to lysis by activated macrophages.
Patent - Published U.S. Patent Application # 20040191761; Published International Patent Application WO 2004087886.
Publication - Routes, et al. J Exp Med. 2005 Dec 5;202(11):1477-82.
Inventors - John M. Routes, MD
Licensing Status - This technology is available for licensing.
For Further Information, Contact:
Emmanuel Hilaire, PhD
Technology Transfer Office
National Jewish Health
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Denver, CO 80206
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