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Increased Therapeutic Effectiveness of PE-Based Immunotoxins

Keywords: Therapeutic, cancer, chemotherapy, immunotoxin, immunogenic epitopes, human B-cell epitopes, Pseudomonas Exotoxin A (PE).

Summary: 
The Laboratory of Molecular Biology of the National Cancer Institute seek parties interested in collaborative research to co-develop and commercialize immunotoxins using toxin domains lacking human B-cell epitopes.

Technology: 
Patients receiving immunotoxin cancer therapy are less likely to experience the deleterious side-effects associated with non-discriminate therapies such as chemotherapy or radiation therapy. Unfortunately, the continued administration of immunotoxins often leads to a reduced patient response due to the formation of neutralizing antibodies against immunogenic epitopes contained within Pseudomonas exotoxin A (PE). 

To improve the therapeutic effectiveness of PE-based immunotoxins through multiple rounds of drug administration, NIH inventors have sought to identify and remove the human B-cell epitopes within PE. Previous work demonstrated that the removal of the murine B-cell and T-cell epitopes from PE reduced the immunogenicity of PE and resulted in immunotoxins with improved therapeutic activity.

This technology involves the identification and removal of major human B-cell epitopes on PE by mutation or deletion. Considering these immunotoxins will be administered to humans, the removal of human immunogenic epitopes is important.  The resulting PE-based immunotoxins have increased resistance to the formation of neutralizing antibodies, and are expected to have improved therapeutic efficacy.

Potential Commercial Applications:

• Treatment of diseases associated with increased or  preferential expression of a specific cell surface receptor such as  hematological cancers, lung cancer, ovarian cancer, breast cancer, and head and neck cancers

Competitive Advantages:

• PE variants now include the removal of human B-cell epitopes, further reducing the formation of neutralizing antibodies against  immunotoxins which contain the PE variants
• Less immunogenic immunotoxins result in improved therapeutic efficacy by permitting multiple rounds of administration in humans
• Targeted therapy decreases non-specific killing of healthy, essential cells, resulting in fewer non-specific side-effects and healthier patients

Development Stage: Discovery

Patent Status:  U.S. Provisional Application No. 61/535,668.

Related Technologies:   

• PCT Patent Publication WO 2011/032022 (HHS technology reference E-269-2009/0-PCT-02)
• US Patent Publication US 20100215656 A1 (HHS technology reference E-292-2007/0-US-06)
• US Patent Publication US 20090142341 A1 (HHS technology reference E-262-2005/0-US-06)
• Multiple additional patent families

Contact: Please submit an information request form at  http://techtransfer.cancer.gov or contact
John Hewes, Ph.D., Tel.: (301) 435-3121 or email: hewesj@mail.nih.gov.

Last updated: 08/02/2012

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