CD123-specific chimeric antigen receptor redirected T cells and methods of their use

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United States of America Patent

PATENT NO 9657105
APP PUB NO 20140271582A1
SERIAL NO

13844048

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ATTORNEY / AGENT: (SPONSORED)

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Abstract

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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 5.0×106 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.

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Patent Owner(s)

  • CITY OF HOPE

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Inventor(s)

Inventor Name Address # of filed Patents Total Citations
Brown, Christine E Duarte, US 32 44
Forman, Stephen Duarte, US 4 201
Jonnalagadda, Uma Maheswara Rao Troy, US 5 13
Mardiros, Armen Glendale, US 8 55

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