Genetically Engineered Hematopoietic Stem Cells Deliver TGF-β Inhibitor to Enhance Bone Metastases Immunotherapy.

ABSTRACT: Owing to the immune microenvironment of bones and low selectivity of the drug, patients with bone metastases often respond poorly to immunotherapy. In this study, programmed cell death protein 1 (PD1)-expressing hematopoietic stem cells (HSCs) are genetically engineered for bone-targeted delivery of the transforming growth factor beta (TGF-β) small-molecule inhibitor SB-505124 (SB@HSCs-PD-1). Intriguingly, compared to anti-PD-L1 monoclonal antibodies, as "living drugs", HSCs-PD-1 not only show great targeting ability to the bone marrow, but are also able to reduplicate themselves within the bone marrow niche and continuously express PD-1 molecules. The SB released from HSCs-PD-1 competitively bound to TGF-β receptors on CD4⁺ T cells and facilitate CD4⁺ T cell differen

SUBMITTER: Wang B 

PROVIDER: S-EPMC9534984 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature