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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.