Armen Mardiros;Stephen Forman;Uma Maheswara Rao Jonnalagadda;Christine E. Brown
发明人:
Stephen Forman,Armen Mardiros,Christine E. Brown,Uma Maheswara Rao Jonnalagadda
申请号：
US13844048
公开号：
US09657105B2
申请日:
2013.03.15
申请国别(地区):
US
年份:
2017
代理人:
摘要：
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.
