Development of TRX518, an aglycosyl humanized monoclonal antibody (Mab) agonist of huGITR.

e13028 Background: Glucocorticoid-induced tumor necrosis factor receptor (GITR) is expressed on several cell types, including regulatory and effector T cells, B cells, NK cells, and antigen-presenting cells. In murine models, our agonistic anti-mouse (m) GITR antibody was a robust vaccine adjuvant and, in combination with chemotherapy, significantly reduced tumor burden and prolonged survival compared with antibody or chemotherapy alone. The anti-mGITR Mab enhanced effector T cell responses and ablation of T regulatory cell-mediated suppression. A similar effect was observed when a chimeric anti-human (hu) GITR Mab (Ch-6C8-Agly) was used in nonhuman primates (NHP). NHP treated with anti-huGITR had augmented humoral and cellular immune responses compared with controls. Mab treatment was well tolerated with no observed adverse events. Methods: TRX518, a fully humanized IgG1 anti-huGITR Mab, was constructed. In addition to humanization, heavy chain asparagine 297 was substituted with alanine to eliminate N-l...