Jan 8, 2021 · Mechanistic studies revealed that autocrine IFN-α/β upregulated TRAIL expression on activated T cells to elicit MDSC apoptosis via the TRAIL–DR5 interaction and acted synergistically with TNF-α...

Feb 1, 2021 · Myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes with potent immunosuppressive activity. They are implicated in the regulation of immune...

The expression of DR5, a TRAIL-R, was significantly higher in MDSC derived from tumor-bearing mice compared to control mice. Furthermore, MDSC derived from DR5 KO mice showed increased survival compared to WT MDSC.

Dr5 KO MDSCs had significantly lower apoptosis after a 3-hour culture and significantly higher survival after overnight incubation than WT MDSCs (Figure 3, C and D), indicative of an important role of DR5 in MDSC survival. To verify these observations, we performed experiments using mixed BM chimera.

This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a new monoclonal antibody potent DR5 agonist, DS-8273a, in subjects with advanced solid tumors. Methods The study comprised dose …

In mice, agonistic DR5 antibody potentiated the effect of immune checkpoint blockade (CTLA-4 targeting antibody), which resulted in a 5-fold decrease of the tumor growth (15). This suggests that TRAIL-R targeting antibody can be potentially used in …

Oct 13, 2022 · Death receptor 5 (DR5), a receptor of TNF-related apoptosis-inducing ligand (TRAIL), was highly expressed on MDSCs and cancer cells; targeting DR5 using agonistic anti-DR5 antibody (MD5-1) specifically depleted MDSCs and induced enrichment of CD8 + T lymphocytes in tumors and exhibited stronger tumor inhibition efficacy in immune-competent mice ...

Jul 13, 2015 · Recently, it was shown that selective upregulation of TRAIL receptor DR5 on mouse MDSCs and downregulation of decoy receptors DCR1 and DCR2 in human MDSCs make TRAIL receptor targeting a viable and specific method of MDSC depletion.

The negative regulatory domain co-targeting with dual-specificity antibody designs elicits sustained DR5 clustering and a superior anti-tumor response, explaining past clinical failures and revisiting future clinical strategies.

Cimetidine promotes MDSC apoptosis and inhibits lung cancer cell proliferation by inducing Fas/FasL expression on the surface of MDSCs. IFN-α/β upregulates TRAIL expression on T cells and enhances the inhibitory effect of TNF-α on MDSC through the TRAIL-DR5 pathway.