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filingDate 2017-05-22-04:00^^<http://www.w3.org/2001/XMLSchema#date>
grantDate 2020-05-26-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_b07917960125abfb63aca302e0a8435f
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publicationDate 2020-05-26-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber US-10660916-B2
titleOfInvention CD123-specific chimeric antigen receptor redirected T cells and methods of their use
abstract A family of chimeric antigen receptors (CARs) containing a CD123 specific scFv was developed to target different epitopes on CD123. In some embodiments, such a CD123 chimeric antigen receptor (CD123CAR) gene includes an anti-CD123 scFv region fused in frame to a modified IgG4 hinge region comprising an S228P substitution, an L235E substitution, and optionally an N297Q substitution; a costimulatory signaling domain; and a T cell receptor (TCR) zeta chain signaling domain. When expressed in healthy donor T cells (CD4/CD8), the CD123CARs redirect T cell specificity and mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. Further, T cells obtained from patients with active AML can be modified to express CD123CAR genes and are able to lyse autologous AML blasts in vitro. Finally, a single dose of 5.0×10 6 CAR123 T cells results in significantly delayed leukemic progression in mice. These results suggest that CD123CAR-transduced T cells may be used as an immunotherapy for the treatment of high risk AML.
priorityDate 2013-03-15-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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