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CD45-directed CAR-T cells with CD45 knockout
- Development stage
- Preclinical
- Lead developer
- University Medical Center Hamburg-Eppendorf
- Modality
- CRISPR-Cas9 → CRISPR Systems → Programmable Nucleases → Gene Editing → Gene Therapies, CAR-T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies
- Administration
- Intravenous
01
Overview
CD45-directed CAR-T cells with CD45 knockout is an investigational autologous chimeric antigen receptor (CAR) T-cell therapy designed to target CD45-expressing hematological malignancies, such as acute myeloid leukemia (AML) and lymphoma. CD45 (receptor-type tyrosine-protein phosphatase C) is a pan-hematopoietic antigen expressed on almost all nucleated white blood cells, making it a highly attractive target for universal blood cancer therapy and targeted conditioning regimens prior to hematopoietic stem cell transplantation (HSCT). To overcome the challenge of fratricide (self-killing) caused by the high expression of CD45 on T cells, CRISPR/Cas9 ribonucleoproteins (RNPs) are used to knock out the endogenous CD45 gene in the effector T cells prior to retroviral transduction with a third-generation CD45-directed CAR. This modification prevents fratricide without impairing the in vitro proliferation, activation, or cytotoxic functionality of the CAR-T cells.
- Other names
- CD45ko/CD45CAR-TCD45ko/CD45CAR-T cellsCD45koCD45-CAR-TCD-45koCD45-CAR-TCD 45koCD45-CAR-TCD45koCD45CAR-TCD-45koCD45CAR-TCD 45koCD45CAR-T
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