CD5-CAR-γδ T cells

CD5-CAR-γδ T cells (also referred to as mRNA-engineered CD5-CAR-γδTCD5− cells) are an experimental allogeneic chimeric antigen receptor (CAR) T-cell therapy being investigated for the treatment of T-cell acute lymphoblastic leukemia (T-ALL). This therapy utilizes gamma-delta (γδ) T cells derived from healthy donors as the cellular backbone, which offers an off-the-shelf approach and minimizes the risk of graft-versus-host disease (GvHD). The CAR construct is engineered to target CD5, a surface antigen highly expressed on malignant T-ALL cells, using a CD5-specific nanobody (VHH) as the antigen-binding domain. To prevent fratricide (self-destruction among the engineered cells), the CD5 gene is knocked out in the γδ T cells using CRISPR/Cas9 technology prior to CAR engineering. The CAR construct is delivered via in vitro transcribed (IVT) mRNA through electroporation, providing a transient expression profile that enhances safety by avoiding genomic integration and reducing long-term off-tumor toxicity. Preclinical studies have demonstrated that these cells exhibit potent cytotoxicity against CD5-positive malignant T-cell lines and significant antitumor efficacy in xenograft mouse models.

Other names

CD5-CAR-γδTCD5− cells