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TRAC-integrated 41BB BCMA CAR-T
- Development stage
- Preclinical
- Lead developer
- University of California, San Francisco
- 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
TRAC-integrated 41BB BCMA CAR-T is an experimental chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA), primarily investigated for the treatment of multiple myeloma. This therapy utilizes CRISPR/Cas9 genome editing to precisely integrate the CAR transgene into the T-cell receptor alpha constant (TRAC) locus. This site-specific integration results in the knockout of the endogenous T-cell receptor (TCR), which minimizes the risk of graft-versus-host disease (GvHD) and ensures uniform CAR expression under the control of the endogenous TRAC promoter. The construct features a 4-1BB (CD137) costimulatory domain, which is typically associated with enhanced T-cell metabolic fitness and long-term persistence. In preclinical studies, this construct has served as a benchmark for evaluating next-generation CAR-T modifications, such as the 1XX-modified CD3ζ signaling domain. The manufacturing process is designed to be fully non-viral, utilizing electroporation for the delivery of CRISPR components and DNA templates.
- Other names
- TRAC-targeted 41BB BCMA CAR-TTRAC-targeted41BB BCMA CAR-TTRAC-targeted-41BB BCMA CAR-TTRAC-knockout 41BB BCMA CAR-TTRAC-knockout41BB BCMA CAR-TTRAC-knockout-41BB BCMA CAR-T
02
Targets
BCMA (B-cell maturation antigen)
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