CD40 agonist-induced IL-12p40 potentiates hepatotoxicity.

ABSTRACT:

Background

CD40 is a compelling target for cancer immunotherapy, however, attempts to successfully target this pathway have consistently been hampered by dose-limiting toxicity issues in the clinic that prevents the administration of efficacious doses.

Methods

Here, using cytokine and cytokine receptor depletion strategies in conjunction with a potent CD40 agonist, we investigated mechanisms underlying the two primary sources of CD40 agonist-associated toxicity, hepatotoxicity and cytokine release syndrome (CRS).

Results

We demonstrate that CD40 agonist -induced hepatotoxicity and CRS are mechanistically independent. Historical data have supported a role for interleukin-6 (IL-6) in CRS-associated wasting, however, our findings instead show that an inflammatory cytokin

SUBMITTER: Bonnans C 

PROVIDER: S-EPMC7264827 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature