TAR-1: a human single chain antibody for the treatment of cancer related to mutations in p53

The Invention TAR-1, a human single chain antibody, which recognizes the common epitope exposed in mutant p53, but not in wild type p53, has been isolated. Binding of TAR-1 to the mutant p53 common epitope restores both the wt conformation and function of p53, and thus restores its ability to bind specifically to DNA and/or abolishes the distinct oncogenic properties of the p53 mutant protein. TAR-1 binds the mutant p53 either in the cytoplasm or in the nucleus of tumor cells and serve as a “broad spectrum” agent for tumor immunotherapy The Need Mutant p53 exerts distinct oncogenic properties and is present in a wide range of tumor cells. It is an obvious therapeutic target that has, so far, failed to yield an approved therapy. The mainstay of much cancer therapy relies on antimetabolites that inhibit DNA synthesis and tumor growth. New approaches that are specific for cancer tissue while leaving the normal tissues unharmed and not plagued with problems owing to resistance are desperately sought Potential Applications TAR-1 offers a novel immunotherapeutic approach for the treatment of cancers whose etiology is related to a mutation in the p53 gene Advantages Broadly applicable – possibly in up to 90% of tumors Highly tumor specific Restores normal p53 conformation and function Interferes with the oncogenic properties of the mutant protein Protein approach: nucleus-directed delivery signal
Stage Cellular model

Binds the mutant p53 epitope with high affinity, in the nM range Binds differentially mutant p53 according to the severity of their conformational change, which determines the extent of the mutant p53 epitope exposure Drives cells expressing mutant p53 into apoptosis Enhances susceptibility of cells expressing mutant p53 to treatment with chemotherapeutic drugs Innhibit colony formation in cells expressing mutant p53 Animal model

iv and it administration of TAR-1 leads to inhibition of human mutant p53 tumor xenografts in mice
Tech Transfer Officer Ms. Irit Ben-Chlouch Office: +972-3-6406601 Fax: +972-3-6406675 Mail: [email protected]

Inventor(s): Beka Solomon

Type of Offer: Licensing



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