Potent and conditional redirected T cell killing of tumor cells using Half DVD-Ig
2017
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. Grinnell | Edit Tarcsa | Charles Hutchins | Tariq Ghayur | Jijie Gu
Abstract 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-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig 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-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.
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