,Potent and conditional redirected T cell killing of tumor cells using Half DVD-Ig

• 作 者: Philip D. Bardwell Matthew M. Staron Junjian Liu Qingfeng Tao Susanne Scesney Gail Bukofzer Luis E. Rodriguez Chee-Ho Choi Jennifer Wang Qing Chang Feng Dong Cherrie Donawho Jieyi Wang Christine M. Gr
• 机 构: Foundational Immunology, AbbVie Bioresearch Center, Worcester, MA 01605, USA“,” Torque Therapeutics
• 出 处: 蛋白质与细胞
• 发表日期: 2018年1期
• 关键词: DVD-lg Half DVD-lg Halfbody epidermal growth factor receptor redirected T-cell c

Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-lg format that can redirect CTL to kill tumor cells. Notably, Half DVD-lg molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-lg molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.