Antibody targeting tumor-derived soluble NKG2D ligand sMIC provides dual co-stimulation of CD8 T cells and enables sMIC⁺ tumors respond to PD1/PD-L1 blockade therapy.

ABSTRACT:

Background

Insufficient co-stimulation accounts for a great deal of the suboptimal activation of cytotoxic CD8 T cells (CTLs) and presumably unsatisfactory clinical expectation of PD1/PD-L1 therapy. Tumor-derived soluble NKG2D ligands are associated with poor clinical response to PD1/PD-L1 blockade therapy in cancer patients. One of the mostly occurring tumor-derived soluble NKG2D ligands, the soluble MHC I chain related molecule (sMIC) can impair co-stimulation to CD8 T cells. We investigated whether co-targeting sMIC can provide optimal co-stimulation to CTLs and enhance the therapeutic effect of PD1/PD-L1 blockades.

Methods

Single agent therapy of a PD1/PD-L1 blockade antibody or a sMIC-targeting non-blocking antibody or a combination therapy of the two antibodies were im

SUBMITTER: Zhang J 

PROVIDER: S-EPMC6709558 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature