Improving the Therapeutic Effectiveness of Foreign Proteins
Posted Jun 22 2010 5:00pm
Description of Invention: Foreign proteins are recognized by the immune system, which typically responds by creating neutralizing antibodies to the foreign protein. While this is helpful in response to an infection or the administration of a vaccine, it is troublesome when foreign proteins are administered for the treatment of disease in a non-vaccine capacity (e.g., an immunotoxin, therapeutic antibody, protein replacement therapy, etc.). These neutralizing antibodies decrease the therapeutic effectiveness of the protein, ultimately resulting in the inability to administer the foreign protein to a patient with any benefit. Thus, if a particular disease requires multiple administrations, the chance of achieving a successful response with the foreign protein becomes unlikely.
A particular instance where neutralizing antibodies have reduced therapeutic effectiveness is the use of immunotoxins for treatment of cancer. Immunotoxins comprise an antibody domain for targeting a surface antigen on a cancer cell and a toxin domain that is capable of killing the targeted cell. The toxin domain is typically a modified form of a bacterial toxin, such as Pseudomonas exotoxin A, and is therefore recognized as a foreign protein by the patient's immune system. Although immunotoxins have an initial therapeutic effect, the effectiveness is ultimately mitigated by neutralizing antibodies against the toxin domain of the immunotoxin. Thus there is a clear need to reduce the formation of neutralizing antibodies in patients who are administered a foreign protein like an immunotoxin.
This technology addresses this need by reducing the formation of neutralizing antibodies through the co-administration of the immunosuppressive agent CP-690,550 with a therapeutic foreign protein. Specifically, the inventors found that co-administering CP-690,550 and an immunotoxin to a mouse model reduced the production of neutralizing antibodies to the immunotoxin. These results suggest that the use of CP-690,550 in combination with any foreign protein therapeutic could allow multiple cycles of therapy and result in improved therapeutic efficacy.
Improved efficacy of treatments that utilize the foreign proteins that can be neutralized by patient immune systems
Administration of CP-690,550 with an immunotoxin, for the treatment of cancers such as mesothelioma, lung cancer, leukemia, lymphoma, ovarian cancer, etc.
Broad applicability to any treatment where a foreign protein is used as a therapeutic agent
Overcomes a persistent challenge to the use of protein biologics as therapeutics
Reduction of the immune response by a patient reduces the production of neutralizing antibodies, increasing the success rate of the treatment
Fewer neutralizing antibodies increases the duration in which a foreign protein can achieving a therapeutic concentration
Fewer neutralizing antibodies also allows multiple rounds of effective administration of the foreign protein
Longer duration for a therapeutic concentration and the ability to administer multiple doses increase the chances of a therapeutic response
Development Status: Preclinical stage of development; preliminary mouse model data
Pastan et al. PCT Publication WO 2009/032954 "Deletions in Domain II of Pseudomonas Exotoxin A that Reduce Non-Specific Toxicity"
Pastan et al. US Patent Publication 2009/0142341 "Mutated Pseudomonas Exotoxins with Reduced Antigenicity"
Changelian et al. Science 2003 Oct 31;302(5646):875-878. "Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor." [ PubMed: 14593182 ]
Pastan et al. US Patent 7,355,012 "Mutated Anti-CD22 Antibodies with Increased Affinity To CD22 Expressing Leukemia Cells"
Licensing Status: Available for licensing.
Collaborative Research Opportunity: The Center for Cancer Research, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or firstname.lastname@example.org for more information. Click here to view the NCI collaborative opportunity announcement.
Portfolios: Cancer Cancer - Therapeutics Internal Medicine Internal Medicine - Therapeutics
For Additional Information Please Contact: David Lambertson Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: email@example.com Phone: 301-435-4632 Fax: 301-402-0220