Increased Therapeutic Effectiveness of PE-Based Immunotoxins
chemotherapy, immunotoxin, immunogenic epitopes, human B-cell
epitopes, Pseudomonas Exotoxin A (PE).
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.
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
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
- 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
- Targeted therapy decreases non-specific killing of healthy,
essential cells, resulting in fewer non-specific side-effects and
Application No. 61/535,668.
- PCT Patent Publication WO 2011/032022 (HHS technology reference
- US Patent Publication US 20100215656 A1 (HHS technology
- US Patent Publication US 20090142341 A1 (HHS technology
- Multiple additional patent families
Please submit an information
request form at http://techtransfer.cancer.gov
John Hewes, Ph.D., Tel.: (301) 435-3121 or email: firstname.lastname@example.org
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