Engineered soluble, trimerized 4-1BBL variants as potent immunomodulatory agents.

ABSTRACT: Targeting co-stimulatory receptors promotes the activation and effector functions of anti-tumor lymphocytes. 4-1BB (CD137/TNFSF9), a member of the tumor necrosis factor receptor superfamily (TNFR-SF), is a potent co-stimulatory receptor that plays a prominent role in augmenting effector functions of CD8⁺ T cells, but also CD4⁺ T cells and NK cells. Agonistic antibodies against 4-1BB have entered clinical trials and shown signs of therapeutic efficacy. Here, we have used a T cell reporter system to evaluate various formats of 4-1BBL regarding their capacity to functionally engage its receptor. We found that a secreted 4-1BBL ectodomain harboring a trimerization domain derived from human collagen (s4-1BBL-Tri_XVIII) is a strong inducer of 4-1BB co-stimulation.

SUBMITTER: Battin C 

PROVIDER: S-EPMC10412504 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature