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

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.

SUBMITTER: Bardwell PD

PROVIDER: S-EPMC5777973 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Bardwell Philip D PD Staron Matthew M MM Liu Junjian J Tao Qingfeng Q Scesney Susanne S Bukofzer Gail G Rodriguez Luis E LE Choi Chee-Ho CH Wang Jennifer J Chang Qing Q Dong Feng F Donawho Cherrie C Wang Jieyi J Grinnell Christine M CM Tarcsa Edit E Hutchins Charles C Ghayur Tariq T Gu Jijie J

Protein & cell 20170605 1

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 demons ...[more]

PMID: 28585177

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