4-1BB agonist targeted to fibroblast activation protein α synergizes with radiotherapy to treat murine breast tumor models.

ABSTRACT:

Background

Ionizing radiation (IR) is a double-edged sword for immunotherapy as it may have both immunosuppressive and immunostimulatory effects. The biological effects of IR on the tumor microenvironment (TME) are a key factor for this balance. Fibroblast activation protein (FAP) is expressed on the surface of cancer-associated fibroblasts (CAF) in many cancer types and its abundance is associated with the poor immune response to immune-checkpoint-blockade in patients. We hypothesized that IR increases FAP expression in CAFs, therefore the combination of IR with targeted immunomodulators such as an agonistic anti-FAP-4-1BBL fusion protein could enhance the immune-mediated antitumoral effects of these treatments.

Methods

The murine transplantable TS/A tumor-cell-line co-engr

SUBMITTER: Garate-Soraluze E 

PROVIDER: S-EPMC11815443 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature