LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells.

ABSTRACT:

Background

The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved. This study tested whether the overexpression of Lectin-like transcript 1 (LLT1), an NK cell inhibitory ligand, in T cell receptor (TCR) and HLA-I/II disrupted universal CD38-targeting CAR-T cells could prevent rejection by allogeneic NK cells.

Methods

We generated CD38-targeting univer

SUBMITTER: Zhu S 

PROVIDER: S-EPMC11763111 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature