A TCR-mimic antibody to WT1 bypasses tyrosine kinase inhibitor resistance in human BCR-ABL+ leukemias

Author:

Dubrovsky Leonid12ORCID,Pankov Dmitry13,Brea Elliott Joseph14,Dao Tao1,Scott Andrew1,Yan Su5,O’Reilly Richard J123,Liu Cheng5,Scheinberg David A.14

Affiliation:

1. Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, New York, NY;

2. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY;

3. Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY;

4. Weill Cornell Medical College, New York, NY; and

5. Eureka Therapeutics, Emeryville, CA

Abstract

Key Points This study shows the effective anticancer activity of a T-cell receptor mimic antibody targeting WT1 in resistant human Ph+ ALL. In combination with tyrosine kinase inhibitors, ESKM can result in cure of Ph+ ALL in murine models.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference41 articles.

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2. Alternative splicing and genomic structure of the Wilms tumor gene WT1.;Haber;Proc Natl Acad Sci USA,1991

3. Expression, purification, and characterization of the 4 zinc finger region of human tumor suppressor WT1.;Nurmemmedov;Protein Expr Purif,2006

4. The candidate Wilms’ tumour gene is involved in genitourinary development.;Pritchard-Jones;Nature,1990

5. The Wilms’ tumor gene product WT1 activates or suppresses transcription through separate functional domains.;Wang;J Biol Chem,1993

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