City of Hope

Kite Pharma, Inc.

Umamaheswararao Jonnalagadda

Armen Mardiros

Christine E. Brown

Stephen J. Forman

Jonnalagadda, Umamaheswararao

Mardiros, Armen

Forman, Stephen J.

Brown, Christine E.

Stephen J Forman

Christine E Brown

Ruben Alvarez Rodriguez

Uma Maheswara Rao Jonnalagadda

The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered TCR and/or CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

CD70 binding molecules and methods of use thereof

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 5.0×10CAR123 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.

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

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&#xd7;10CAR123 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.

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

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Duarte, CA, United States of America

Armen Mardiros