LCK-knockout allogeneic CAR-T cells

LCK-knockout allogeneic CAR-T cells (also known as disLCK-CAR-T or DISK CAR-T) represent an innovative platform for off-the-shelf allogeneic chimeric antigen receptor (CAR) T-cell therapy. Developed by researchers at the National University of Singapore and Augusta University, this platform addresses the risk of Graft-versus-Host Disease (GVHD) by knocking out the lymphocyte-specific protein tyrosine kinase (LCK), an essential mediator of T-cell receptor (TCR) signaling, rather than knocking out the TCR complex itself (such as via TRAC knockout). While LCK deletion completely abrogates endogenous TCR signaling and prevents GVHD, second-generation CD28-containing CARs remain functional by signaling through the alternative Src family kinase FYN. This selective signaling preservation allows LCK-knockout CAR-T cells to maintain robust anti-tumor efficacy, demonstrate superior in vivo persistence, show reduced exhaustion, and promote a memory-like phenotype in both liquid and solid tumor models.

Other names

DISK CAR-TDISK CAR-T cellsdisLCK-CAR-TdisLCK-CAR-T cellsLCK-disrupted CAR-T cellsLCK-knockout CAR-T cellsLCK-KO CAR-T cells