Unexpected PD-L1 Immune Evasion mechanism in TNBC, Ovarian and other Solid Tumors by DR5 Agonists

ABSTRACT: Lack of effective immune infiltration represents a significant barrier to immunotherapy in solid tumors. Thus, solid tumor-enriched death receptor-5 (DR5) activating antibodies, which generates tumor debulking by extrinsic apoptotic cytotoxicity remains a crucial alternate therapeutic strategy. Over past few decades, many DR5 antibodies moved to clinical trials after successfully controlling tumors in immunodeficient tumor xenografts. However, DR5 antibodies failed to significantly improve survival in phase-II trials, leading in efforts to generate second generation of DR5 agonists to supersize apoptotic cytotoxicity in tumors. Here we have discovered that clinical DR5 antibodies activate an unexpected immunosuppressive PD-L1 stabilization pathway, which potentially had contributed to thei

SUBMITTER: Dr. Tanmoy Mondal 

PROVIDER: S-SCDT-EMM-2020-12716 | biostudies-other |

REPOSITORIES: biostudies-other