A bispecific antibody targeting PD-L1/TNFR2 increases tumor targeting and enhances antitumor efficacy in colorectal cancer.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICIs) have shown limited efficacy in colorectal cancer (CRC), largely due to immunosuppressive tumor microenvironment (TME) including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Additionally, the off-target effects of ICIs can reduce drug accumulation in tumor tissues and lead to immune-related adverse events, further compromising their clinical utility.

Methods

Using knob-into-hole technology, we developed ATAPL1, a bispecific antibody targeting both programmed death-ligand 1 (PD-L1) and tumor necrosis factor receptor 2 (TNFR2). In multiple subcutaneous and orthotopic CRC mouse models, ATAPL1 was evaluated for its tumor targeting, antitumor efficacy, immunomodulatory effects within the TME, and potential

SUBMITTER: Kang X 

PROVIDER: S-EPMC12625873 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature