Multiple CD123 CARs that contain a CD20 safety switch for treatment of AML (SJ-19-0025)

St. Jude Reference #SJ-19-0025

Description

Treatment of Acute Myeloid Leukemia (AML) is challenging due to its high treatment related morbidity and mortality, as well as a high relapse rate. Finding the best targetable antigen for AML has proven challenging due to the high degree of antigen expression overlap between AML blasts and normal hematopoietic cells (HPC) or mature neutrophils.

CD123 is overexpressed on a large proportion of malignant myeloid blasts, with restricted expression on normal cells. Researchers at St. Jude successfully generated a panel of 5 CD123 CAR constructs that were also engineered to co-express CD20, allowing the in vivo destruction of the CAR T cells with the FDA-approved CD20 antibody Rituxan to protect against toxicity. St. Jude is currently conducting a phase I clinical trial on one of the constructs to test safety and maximum tolerated dose.

CD123-CAR T cells can be used to treat CD123-positive tumors, including but not limited to CD123+ acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). This invention can also be used to target normal cells that express CD123, including but not limited to hematopoietic progenitor cells as part of conditioning regimen for a hematopoietic cell transplant (HCT).

Keywords

Acute Myeloid Leukemia (AML), relapse, antigen, AML blasts, hematopoietic cells (HPC), mature neutrophils, CD123, CD20 antibody Rituxan, toxicity, hematopoietic cell transplant (HCT).

Granted Patents or Published Applications

Application filed, available under confidentiality

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