GITRL, (Glucocorticoid-Induced Tumor Necrosis Factor Receptor Ligand, TNFSF18) is a member of the TNF family of ligands and naturally exists as a membrane-anchored type II protein that self assembles as a trimer. GITRL activates the co-stimulatory receptor GITR. A novel single-gene linkerless GITRL trimer was shown to be functional when fused to either the N- or C-terminus of an immunoglobulin Fc domain, offering a flexible strategy that may also be amenable to the production of bispecific agents. GITRL-Fc activated GITR signaling more effectively than prototype GITR agonist antibody DTA-1. GITRL-Fc promoted a robust anti-tumor immune response in several murine tumor graft models, including the apparent total regression of some treated tumors. GITRL-Fc potentiated tumor specific T-cell responses, particularly of the Th1 type, increased antigen-specific CD8 response, and promoted a reduction in Treg-mediated immune-suppressive activity.

Citation Format: Fumiko Axelrod, Hyun-Bae Jie, Erin Mayes, Jorge Monteon, Minu Srivastava, Rui Yun, Inkyung Angie Park, Austin Gurney. GITRL-Fc, an immunotherapeutic agent that stimulates T-cell-mediated antitumor immune response. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A058.