Potent and conditional redirected T cell killing of tumor cells using Half DVD-Ig. Issue 1 (5th June 2017)

• Record Type: Journal Article
• Authors: Bardwell, Philip D; Staron, Matthew M; Liu, Junjian; Tao, Qingfeng; Scesney, Susanne; Bukofzer, Gail; Rodriguez, Luis E; Choi, Chee-Ho; Wang, Jennifer; Chang, Qing; Dong, Feng; Donawho, Cherrie; Wang, Jieyi; Grinnell, Christine M; Tarcsa, Edit; Hutchins, Charles; Ghayur, Tariq; Gu, Jijie
• Is Part Of: Protein & cell. Volume 9:Issue 1(2018)
• Page Start: 121
• Page End: 129
• Publication Date: 2017-06-05
• Subjects: DVD-Ig -- Half DVD-Ig -- Halfbody -- epidermal growth factor receptor -- redirected T-cell cytotoxicity -- rCTL; Proteins -- Periodicals; Cells -- Periodicals; Cytology -- Periodicals; 572.6
• DOI: 10.1007/s13238-017-0429-z
• Languages: English
• ISSNs: 1674-800X

Abstract

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.