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Immunotoxin for the Treatment of Neuroblastoma Relapse

Posted Oct 20 2010 8:00pm

Description of Invention:
Immunotoxins are proteins which have two distinct domains: (1) an antibody or antibody binding fragment which is capable of recognizing a single specific cell surface protein and (2) a toxin domain which is capable of inducing cell death. Immunotoxins are currently being pursued as therapeutics because they specifically kill diseased cells while leaving essential, healthy cells alone. This increases the effectiveness of the therapy while reducing the appearance of side-effects. A particular immunotoxin that is being studied in clinical trials consists of an anti-CD22 antibody binding fragment and a mutated Pseudomonas exotoxin A. Although this immunotoxin is being explored primarily as a treatment for hematological malignancies, it can be used to treat any condition where CD22 is overexpressed on the cell membrane of diseased cells.

Neuroblastomas are malignant cancers that start in nerve tissue and primarily affect infants and children. Although frontline treatments for neuroblastoma are often effective, relapse frequently occurs in high risk cases. The most common form of relapse in neuroblastoma patients is caused by Neuroblastoma tumor initiating cells (NB-TIC). Therefore, if NB-TIC could be eliminated, high risk neuroblastoma patients could have a therapeutic option for preventing a relapse.

This invention concerns the discovery that NB-TIC expresses CD22. As a result, NB-TIC are susceptible to treatment with an anti-CD22 immunotoxin. By combining frontline neuroblastoma treatments with anti-CD22 immunotoxins, both the primary neuroblastoma and cells capable of initiating a relapse can be eliminated. As a result, even high risk neuroblastoma patients should have an increased chance of surviving neuroblastoma.

Applications:
Treatment and prevention of neuroblastoma relapse

Advantages:
  • Increased therapeutic effectiveness with decreased non-specific killing of essential, healthy cells
  • Neuroblastoma relapse commonly begins in the bone marrow, an environment which is accessible to immunotoxins
  • Combined treatment addresses both the tumor and the cause of relapse, leading to more efficient treatments than frontline therapeutics alone


Development Status:
Preclinical stage of development for treatment of neuroblastoma relapse; immunotoxins have clinical data associated with treatment of hematological malignancies

Inventors:
Carol J Thiele (NCI)


Patent Status:
HHS, Reference No. E-204-2010/0
US, Application No. 61/356,202 filed 18 Jun 2010


Relevant Publication:
  1. US Patent 7,355,012 - “Mutated Anti-CD22 Antibodies with Increased Affinity to CD22-Expressing Leukemia Cells” [ View ]
  2. PCT Patent Application WO 2007/016150 - “Mutated Pseudomonas Exotoxins with Reduced Antigenicity” [ View ]
  3. PCT Patent Application WO 2009/032954 - “Deletions in Domain II of Pseudomonas Exotoxin A That Reduce Non-Specific Toxicity [ View ]


Licensing Status:
Available for licensing

Collaborative Research Opportunity:
The Center for Cancer Research, Pediatric Oncology Branch and Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize recombinant anti-CD22 immunotoxins for the treatment of neuroblastoma. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.


Portfolios:
Cancer
Cancer - Therapeutics



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: 2179

Updated: 10/2010

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