Combination of T cell-redirecting strategies with a bispecific antibody blocking TGF-β and PD-L1 enhances antitumor responses.

ABSTRACT: T cell-based immunotherapies for solid tumors have not achieved the clinical success observed in hematological malignancies, partially due to the immunosuppressive effect promoted by the tumor microenvironment, where PD-L1 and TGF-β play a pivotal role. However, durable responses to immune checkpoint inhibitors remain limited to a minority of patients, while TGF-β inhibitors have not reached the market yet. Here, we describe a bispecific antibody for dual blockade of PD-L1 and TFG-β, termed AxF (scFv)₂, under the premise that combination with T cell redirecting strategies would improve clinical benefit. The AxF (scFv)₂ antibody was well expressed in mammalian and yeast cells, bound both targets and inhibited dose-dependently the corresponding signaling pathways in lum

SUBMITTER: Tapia-Galisteo A 

PROVIDER: S-EPMC11018002 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature