Cancer Therapeutic Composed Of Cholera Exotoxin
The National Cancer Institute's Laboratory of Molecular Biology is
seeking parties interested in collaborative research to further
develop, evaluate, or commercialize immunotoxins composed of
cholera exotoxin.
R&D Status: In vitro proof-of-concept
with results similar to immunotoxin analog that was validated in in
vivo models and early clinical trials.
IP Status: U.S. Provisional Application No.
61/058,872 filed 04 June 2008
Immunotoxins represent an important therapeutic tool for the
treatment of cancer because they are able to specifically target
cancer cells while ignoring healthy cells. Many patients treated
with Pseudomonas exotoxin A (PE) based immunotoxins develop
neutralizing antibodies after the first administration. As a
result, only one effective administration of a PE-based immunotoxin
is often possible.
NCI inventors have created a novel immunotoxin, where the toxin
portion is a truncated Cholera exotoxin (cholix toxin). The
cholix toxin is able to overcome the immunogenicity issues
associated with a previous PE-based immunotoxin developed at
NCI. Although cholix toxin retains strong functional and
structural similarity to PE, neutralizing antibodies to PE do not
affect the truncated cholix toxin. As a result, cholix
immunotoxins are of potential utility after a patient has developed
neutralizing antibodies to PE. The ability to deliver two
rounds of immunotoxins to a patient will increase the successful
treatment of various diseases, including cancer. The efficacy
of the cholix toxin has been demonstrated using assays that are
analogous to ones used to validate the PE toxin, which is currently
in clinical trials.
Backgound Literature:
Du X, Beers R, Fitzgerald DJ, Pastan I. Differential cellular
internalization of anti-CD19 and -CD22 immunotoxins results in
different cytotoxic activity. Cancer Res. 2008 Aug 1;68(15):6300-5.
[PMID: 18676854 ]
Pastan I, Hassan R, FitzGerald DJ, Kreitman RJ. Immunotoxin
treatment of cancer.
Annu Rev Med. 2007;58:221-37. [PMID: 17059365]
Further R&D Needed:
- Fuse with other antibody fragments
- In vivo validation of new immunotoxin including pharmacokinetic
studies, anti-tumor experiments and primate studies.
Contact Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Tel: 301-435-3121
Email: hewesj@mail.nih.gov
Please reference advertisement #758
Posted 10/01/2008