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Off-the-Shelf Allogeneic CAR γδ T-Cell Platform
Screenshot 2026-08-30 at 8.39.24 AM
CARTx describes the platform as an off-the-shelf CAR-T approach using healthy-donor γδ T cells genetically engineered with CRISPR/AAV. Its initial programs include CD38KO/CD38-CAR γδ T cells for T-ALL and other CD38-positive hematologic malignancies, and TGFBR2KO/GD2-CAR γδ T cells for high-grade gliomas.

Background

CAR-T therapy has demonstrated significant potential in cancer treatment, while manufacturing complexity, patient-specific production, treatment availability, and expansion into additional malignancies remain important areas of development.

γδ T cells combine characteristics of innate and adaptive immunity and recognize targets in an MHC-independent manner, making them attractive candidates for healthy-donor allogeneic cell-therapy platforms. CARTx is developing this cell type as the basis for standardized off-the-shelf CAR therapies.

Overview

The platform uses healthy-donor γδ T cells that are expanded and genetically engineered through a combination of CRISPR gene editing and AAV-mediated CAR delivery.

The CAR can be inserted at a selected genomic location while simultaneously disrupting an endogenous gene where therapeutically useful. CARTx gives two principal examples:

CD38KO/CD38-CAR γδ T cells — the CD38 locus is disrupted while a CD38-targeting CAR is inserted, creating a fratricide-resistant CAR γδ T-cell product for T-cell malignancies and other CD38-positive cancers.

TGFBR2KO/GD2-CAR γδ T cells — designed to combine GD2 tumor targeting with disruption of TGFBR2 signaling, addressing an immunosuppressive mechanism relevant to solid tumors such as high-grade gliomas.

The underlying platform also allows CAR insertion into a safe-harbor locus when simultaneous knockout of a target gene is unnecessary.

Benefits

  • Off-the-shelf allogeneic platform using healthy-donor γδ T cells
  • Site-directed CAR integration using CRISPR/AAV engineering
  • Ability to combine CAR knock-in and gene knockout in a single engineering strategy
  • Scalable γδ T-cell expansion for multi-patient manufacturing
  • Platform architecture designed for multiple CAR targets
  • Initial programs spanning both hematologic and solid tumors
  • CD38KO/CD38-CAR strategy designed to address CAR-cell fratricide
  • TGFBR2KO/GD2-CAR strategy designed to enhance activity in an immunosuppressive tumor environment
  • In vivo anti-leukemic activity has been reported for CD38KO/CD38-CAR γδ T cells in preclinical research.

CARTx states that its manufacturing approach can expand cells from one healthy donor to approximately 1 billion cells, with the potential to generate doses for multiple patients.

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