Clinical Proof-of-Concept of a Non-Gene Editing Technology Using miRNA-Based shRNA to Engineer Allogeneic CAR T-Cells.

ABSTRACT: With the success of chimeric antigen receptor (CAR) T-cell therapy in B-cell malignancies, efforts are being made to extend this therapy to other malignancies and broader patient populations. However, limitations associated with the time-consuming and highly personalized manufacturing of autologous CAR T-cells remain. Allogeneic CAR T-cell approaches may overcome these challenges but require further engineering to reduce their alloreactivity. As a means to prevent graft-versus-host disease (GvHD) of allogeneic CAR T-cells, we have selected a micro RNA (miRNA)-based short hairpin RNA (shRNA) targeting CD3ζ which efficiently downregulates the expression of the T-cell receptor (TCR) below detection level. We generated allogeneic anti-B-cell maturation antigen CAR T-cells (CYAD-211) that co-ex

SUBMITTER: Lonez C 

PROVIDER: S-EPMC11855736 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature