ABS1055 GB261 (CND261), A NOVEL CD20/CD3 T-CELL ENGAGER, HAS A DIFFERENTIATED SAFETY PROFILE AND POTENTIAL FOR DEVELOPMENT IN AUTOIMMUNE DISEASES

作者：Yali Song, Zhijun Li, Jiawei Li, Zhaoxin Qian, Kai Zhou, L. Fan, Peng Tan, Prithvi Giri, Zhijun Li, Jianjian Jin, Weiping Liu, J. Haddon, Peter N. Morcos, Joline S.J. Lim, P. Wung, Shafqat Inam, Yong Xie, Li T, Jinfang Zhu · 发表于：Annals of the Rheumatic Diseases · 年份：2025 · DOI：10.1016/j.ard.2025.06.906 · 被引用次数：1 · 研究领域：CAR-T cell therapy research

Background: B cells play an important role in the pathogenesis of autoimmune diseases, through the production of autoantibodies, secretion of inflammatory cytokines, antigen presentation and T cell co-stimulation. Anti-CD20 monoclonal antibodies have been used in the treatment of autoimmune disease, however incomplete B cell depletion in tissues is common and associated with non-response. T-cell engagers (TCEs) that deplete B cells are showing early clinical evidence of safety and efficacy for the treatment of autoimmune diseases [1–4]. GB261 (also known as CND261) is a recombinant bispecific antibody against CD20 and CD3, designed with a high affinity CD20 binding domain (KD = 804 pM) and very low CD3 binding affinity (2.00 μM) to maximize B cell depletion while minimizing risk of possible complications of treatment with TCEs, such as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Additionally, GB261 (CND261) has active Fc effector function to kill CD20+ B cells, specifically, but not T cells, via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In line with its molecular design, GB261 (CND261) induced comparable in vitro T cell activation and CD20+ cell killing compared to a benchmark anti-CD20/CD3 bispecific TCE but lower levels of cytokine release [5]. In vivo, GB261 (CND261) caused sustained reductions in peripheral B cells and limited cytokine production in cynomolgus monkey...