Split-design approach enhances the therapeutic efficacy of ligand-based CAR-T cells against multiple B-cell malignancies.

ABSTRACT: To address immune escape, multi-specific CAR-T-cell strategies use natural ligands that specifically bind multiple receptors on malignant cells. In this context, we propose a split CAR design comprising a universal receptor expressed on T cells and ligand-based switch molecules, which preserves the natural trimeric structure of ligands like APRIL and BAFF. Following optimization of the hinges and switch labeling sites, the split-design CAR-T cells ensure the native conformation of ligands, facilitating the optimal formation of immune synapses between target cancer cells and CAR-T cells. Our CAR-T-cell strategy demonstrates antitumor activities against various B-cell malignancy models in female mice, potentially preventing immune escape following conventional CAR-T-cell therapies in the cas

SUBMITTER: Li S 

PROVIDER: S-EPMC11555413 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature