CAR T
Published on May 06, 2025
Insulating HSPCs from autologous CAR33-directed CAR T cells
by Blood Advances
Petty NE, Radtke S, Kanestrom G, et al. Protection of CD33-Modified Hematopoietic Stem Cell Progeny From CD33-Directed CAR T Cells in Nonhuman Primates. Blood Advances. 2025; (doi: 10.1182/bloodadvances.2024015016).
Researchers report the safety of a novel approach to insulate edited cells from chimeric antigen receptor (CAR) selection and attack. This protection is necessary for allogeneic or gene-modified autologous stem cell transplantation to succeed in patients with monogenic disorders. Shielding modified stem cell progeny helps keep engraftment levels above the threshold required for therapeutic viability. To illustrate, two rhesus macaques were engrafted with hematopoietic stem and progenitor cells (HSPCs) edited to wipe out CD33, a surface protein that presents early on HSPCs and on myeloid progenitors. After infusion in the lab subjects, autologous CAR33-directed CAR T cells expanded and triggered specific elimination of CD33+ cells. CD33-modified stem cell progeny were spared, resulting in a transient enrichment for gene-edited cells in the blood. The study authors note that similar engraftment levels were achieved regardless of the type of editing used — CRISPR/Cas9 or adenine base editor.
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