Blockade of TGF-β and PD-L1 by bintrafusp alfa promotes survival in preclinical ovarian cancer models by promoting T effector and NK cell responses.

ABSTRACT:

Background

Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels of transforming growth factor-β (TGF-β) in ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade of TGF-β and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour immune responses in preclinical HGSC models.

Methods

BA is a first-in-class bifunctional inhibitor of TGF-β and PD-L1, and was tested for effects on overall survival and altered TIME in syngeneic HGSC models.

Results

Using a mouse ID8-derived HGSC syngeneic model with IFNγ-inducible PD-L1 expression, BA treatments significantly reduced ascites development and tumour burden. BA treatments depleted TGF-β and VEGF in ascites, and skewed the TIME towards cytotoxicity

SUBMITTER: Kment J 

PROVIDER: S-EPMC11183086 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature