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
1 Foundational Immunology, AbbVie Bioresearch Center, Worcester, MA 01605, USA;
2 Global Preclinical Safety, AbbVie Bioresearch Center, Worcester, MA 01605, USA;
3 Oncology Discovery, AbbVie Inc., North Chicago, IL 60064, USA;
4 DMPK-BA, AbbVie Bioresearch Center, Worcester, MA 01605, USA;
5 Research and Development, AbbVie Inc., North Chicago, IL 60064, USA;
6 Torque Therapeutics Inc., Cambridge, MA 02142, USA;
7 Innovent Biologics Inc., Suzhou, China;
8 Lyvgen Biopharma, Shanghai 201203, China
Received Date: 2017-01-30
Rev Recd Date:2017-05-04
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.Keywords: DVD-Ig,
Half DVD-Ig,
Halfbody,
epidermal growth factor receptor,
redirected T-cell cytotoxicity,
rCTL
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