5 Key Takeaways

• 1

  Researchers developed a two-vector system to deliver CRISPR-Cas9 machinery and DNA templates to generate CAR T cells directly in vivo.

• 2

  The system uses CD3-targeted enveloped delivery vehicles and AAV-hT7, inserting the CAR transgene into the T-cell TRAC locus.

• 3

  In humanized mice, the optimized system generated CAR-expressing cells comprising up to 19.7% of splenic T cells and completely depleted B cells.

• 4

  The treatment produced complete responses in mouse models of B-cell acute lymphoblastic leukemia and multiple myeloma, and showed activity against sarcoma.

• 5

  The platform remains preclinical, and immunodeficient mouse models limited assessment of immunogenicity, biodistribution, and safety.