Inhibition of Interleukin-6 (IL-6) Signaling and Tumor Growth by a Human Neutralizing Anti-IL-6 Antibody with a Prolonged Half-Life

ABSTRACT: Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a major role in responding to injury or infection as well as immune response, inflammation, and hematopoiesis. High levels of circulating IL-6 are observed in many tumor types and are associated with poor outcomes. We show that knockdown of IL-6 or IL-6 receptor (IL-6R) inhibits IL-6 signaling and cell viability. In contrast, over-expression of IL-6 enhances tumor growth in vitro and in vivo, thereby supporting the role of IL-6 in tumorigenesis. We developed a human monoclonal antibody against human IL-6 (MEDI5117) that bears Fc mutations (YTE) to extend its half-life. We tested this antibody in several cancer cell lines that secrete high levels of IL-6, soluble IL-6R, and express gp130. High constitutive pSTAT3 (phosphorylate

ORGANISM(S): Homo sapiens

SUBMITTER: Zheng Liu 

PROVIDER: E-GEOD-62941 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress