Protection of CD33-modified hematopoietic stem cell progeny from CD33-directed CAR T cells in rhesus macaques.

ABSTRACT:

Abstract

The treatment of monogenetic disorders, such as hemoglobinopathies and lysosomal storage diseases, has markedly improved with the advent of cell and gene therapies, particularly allogeneic or gene-modified autologous stem cell transplantations. However, therapeutic efficacy is reliant on maintaining engraftment above a critical threshold. To maintain such engraftment levels, we and others have pursued approaches to shield edited cells from antibody or chimeric antigen receptor (CAR) T-cell-mediated selection. Here, we focused on CD33, which is expressed early on hematopoietic stem and progenitor cells (HSPCs) as well as on myeloid progenitors. Rhesus macaques were engrafted with HSPCs edited to ablate CD33 using either CRISPR/CRISPR-associated protein 9 or adenine base edi

SUBMITTER: Petty NE 

PROVIDER: S-EPMC12141896 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature