PD-L1 directed bispecific Vδ2-T cell engager combines lysis of PD-L1 expressing tumor cells with PD-1 immune checkpoint inhibition and modulation of the tumor immune microenvironment.

ABSTRACT:

Background

Despite the notable success of programmed death ligand 1 (PD-L1)/programmed death 1 (PD-1) immune checkpoint blockade in cancer, resistance remains a substantial challenge. Combining immune checkpoint blockade with direct targeting of effector T cells to tumor cells might improve outcome for a broader spectrum of patients with cancer. Phosphoantigen-responsive Vγ9Vδ2-T cells are potent immune cells that play a pivotal role in tumor immunosurveillance and can coordinate downstream immune activity. Here, we explored whether a Vδ2 bispecific T cell engager (bsTCE) directed against PD-L1 could combine lysis of PD-L1⁺ tumor cells with PD-L1 immune checkpoint blockade.

Methods

PD-L1 specific single domain antibodies (VHHs) were tested for binding to PD-L1 and

SUBMITTER: King LA 

PROVIDER: S-EPMC12574361 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature