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rituximab + CD123-CAR T-cell therapy

Development stage
Unknown
Lead developer
St. Jude Children's Research Hospital
Modality
CAR-T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies, Gene Therapies, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Intravenous
01

Overview

rituximab + CD123-CAR T-cell therapy is an investigational combination treatment regimen and engineered cell therapy product developed by St. Jude Children's Research Hospital. The primary component is a chimeric antigen receptor (CAR) T-cell therapy (either autologous or donor-derived) engineered to target the CD123 antigen (interleukin-3 receptor alpha), which is frequently overexpressed in various hematologic malignancies. The CAR construct utilized in the CATCHAML clinical trial incorporates a 4-1BB costimulatory domain and a CD3-zeta signaling domain to enhance T-cell persistence and anti-tumor activity. A distinctive feature of this therapy is the inclusion of a rituximab-sensitive safety switch, typically a truncated CD20 epitope, expressed on the surface of the engineered T cells. This allows for the administration of the monoclonal antibody rituximab as a pharmacological safety mechanism to selectively and rapidly deplete the CAR T-cells in vivo if the patient experiences severe, life-threatening toxicities such as cytokine release syndrome or neurotoxicity. This combination is currently being evaluated for the treatment of relapsed or refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Other names
rituximab-St. Jude Children's Research Hospital-acute myeloid leukemia-myelodysplastic syndrome-acute lymphoblastic leukemia-blastic plasmacytoid dendritic cell neoplasmRituximab-inducible CD123-CAR T cellsCD123-specific CAR T cellsCD-123-specific CAR T cellsCD 123-specific CAR T cells
02

Targets

CD20 (B-lymphocyte antigen CD20)IL3RA (Interleukin 3 Receptor)

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