CD28-targeted CAR T cells show preclinical activity against T-cell malignancies
Published in Drugs development & discovery, Immunology, Journals.
October 8, 2026 — A peer-reviewed study released today in Nature Communications investigates CD28 as an alternative target for engineered CAR T cells against T-cell cancers.
Semjon Willier, Julian Färber and colleagues found elevated CD28 on T-cell acute lymphoblastic leukaemia (T-ALL) blasts from children and adolescents compared with healthy lymphoid progenitors. They also observed upregulation in nodal T-follicular helper cell lymphomas.
The researchers used CRISPR/Cas9 to remove CD28 from the therapeutic T cells, preventing them from attacking one another. The resulting anti-CD28 CAR T cells selectively killed CD28-positive T-ALL cells and matched anti-CD7 CAR T-cell activity in laboratory and animal experiments.
Compared with the CD7 approach, the CD28 strategy caused less lymphocyte depletion, largely sparing CD8 T cells and natural killer cells while preferentially depleting CD4 subsets. This does not establish safety or efficacy in treated patients: the evidence is preclinical, and loss of normal immune cells remains relevant.
The early accepted article is subject to further editing. Two authors disclose a patent on anti-CD28 CAR T cells.
Source: Willier et al., Nature Communications, October 8, 2026. DOI: 10.1038/s41467-026-78312-3.