Targeting CD28 on T lineage malignancies with chimeric antigen receptor T cells.

Targeting CD28 with CAR T cells effectively kills T-ALL blasts while sparing key immune cells, offering a promising new therapy for T cell malignancies.

• Why it matters: There are no approved immunotherapies for T cell acute lymphoblastic leukemia, and existing approaches face challenges like immune escape and T cell aplasia, highlighting the need for alternative targets.
• What they did: Researchers used CRISPR/Cas9 to knockout CD28 and developed anti-CD28 CAR T cells, testing their efficacy and safety in vitro and in vivo against T-ALL and related lymphomas.
• The result: Anti-CD28 CAR T cells demonstrated comparable tumor-killing ability to anti-CD7 CAR T cells but caused less lymphodepletion, especially sparing CD8 T cells and NK cells, enabling targeted therapy with reduced immune suppression.