Increased Therapeutic Effectiveness of Immunotoxins That Use Toxin Domains Lacking Both T-cell and B-cell Epitopes
Posted Feb 07 2012 7:00pm
Description of Invention: Immunotoxins can kill cancer cells while allowing healthy, essential cells to survive. As a result, patients receiving an immunotoxin 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 B-cell and T-cell epitopes contained within PE. To improve the therapeutic effectiveness of PE-containing immunotoxins through multiple rounds of drug administration, NIH inventors have sought to remove the B-cell and T-cell epitopes within PE. Previous work demonstrated that the removal of the major B-cell epitopes from PE reduced the immunogenicity of PE. This technology involves the identification of major T-cell epitopes on PE, and the removal of the primary T-cell epitope by mutation or deletion. By combining the T-cell epitope mutations with modifications that remove B-cell epitopes, it is possible to create PE-based immunotoxins that have even greater resistance to the formation of neutralizing antibodies. Immunotoxins containing these new PE-variants are expected to have improved therapeutic efficacy.
Applications:
Essential component of immunotoxins
Treatment of any disease associated with increased or preferential expression a specific cell surface receptor
Specific diseases include hematological cancers, lung cancer, ovarian cancer, breast cancer, and head and neck cancers
Advantages:
PE variants now include the removal of both B-cell and T-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
Targeted therapy decreases non-specific killing of healthy, essential cells, resulting in fewer non-specific side-effects and healthier patients
For Licensing Information Please Contact: David Lambertson Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: lambertsond@mail.nih.gov Phone: 301-435-4632 Fax: 301-402-0220
Description of Invention:
Immunotoxins can kill cancer cells while allowing healthy, essential cells to survive. As a result, patients receiving an immunotoxin 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 B-cell and T-cell epitopes contained within PE. To improve the therapeutic effectiveness of PE-containing immunotoxins through multiple rounds of drug administration, NIH inventors have sought to remove the B-cell and T-cell epitopes within PE. Previous work demonstrated that the removal of the major B-cell epitopes from PE reduced the immunogenicity of PE. This technology involves the identification of major T-cell epitopes on PE, and the removal of the primary T-cell epitope by mutation or deletion. By combining the T-cell epitope mutations with modifications that remove B-cell epitopes, it is possible to create PE-based immunotoxins that have even greater resistance to the formation of neutralizing antibodies. Immunotoxins containing these new PE-variants are expected to have improved therapeutic efficacy.
Applications:
Advantages:
Development Status:
Pre-clinical
Inventors:
Ira H Pastan (NCI)
Patent Status:
HHS, Reference No. E-174-2011/0
US, Application No. 61/495,085 filed 09 Jun 2011
Related Technologies:
PCT, Application No. PCT/US2010/048504 filed 10 Sep 2010, Reference No. E-269-2009/0
US, Application No. 12/676,203 filed 04 Sep 2008, Reference No. E-292-2007/0
US, Application No. 11/997,202 filed 25 Jul 2006, Reference No. E-262-2005/0
US, Patent No. 7,081,518, Issued 25 Jul 2006, Reference No. E-139-1999/0
US, Application No. 60/160,071 filed 27 May 1999, Reference No. E-139-1999/0
US, Application No. 60/703,798 filed 29 Jul 2005, Reference No. E-262-2005/0
US, Application No. 60/969,929 filed 04 Sep 2007, Reference No. E-292-2007/0
US, Application No. 61/241,620 filed 11 Sep 2009, Reference No. E-269-2009/0
and multiple additional patent families
For Licensing Information Please Contact:
David Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: lambertsond@mail.nih.gov
Phone: 301-435-4632
Fax: 301-402-0220
Ref No: 2361
Updated: 02/2012