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CD19-CAR-γδTCD5− is an experimental chimeric antigen receptor (CAR) T-cell therapy that utilizes γδ T cells as the cellular backbone. These cells are derived from healthy donors and are genetically modified using CRISPR/Cas9 to knock out the CD5 gene, which is intended to prevent fratricide in CD5-targeted versions or serve as a controlled genetic background. The cells are engineered to express a nanobody-based CAR targeting the CD19 antigen through the electroporation of in vitro transcribed (IVT) mRNA. This construct includes 4-1BB and CD3ζ costimulatory and signaling domains. In preclinical studies, CD19-CAR-γδTCD5− has been used as a control to demonstrate the specificity of CD5-targeted therapies in T-cell acute lymphoblastic leukemia (T-ALL) models. The use of γδ T cells and mRNA-based engineering is designed to provide a safer, allogeneic off-the-shelf therapeutic option with reduced risks of graft-versus-host disease and insertional mutagenesis.
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