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DOI	10.1073/pnas.2104099118
	A functional mammalian display screen identifies rare antibodies that stimulate NK cell–mediated cytotoxicity
	Kang E.; Kadoch C.; Rubenstein J.L.; Lanier L.L.; Wells J.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:31
英文摘要	Therapies that boost the antitumor immune response have shown a great deal of success. Although most of these therapies have focused on enhancing T cell functions, there is a growing interest in developing therapies that can target other immune cell subsets. Like T cells, natural killer (NK) cells are cytotoxic effector cells that play a key role in the antitumor response. To advance the development of NK-based therapies, we developed a functional screen to rapidly identify antibodies that can activate NK cells. We displayed antibodies on a mammalian target cell line and probed their ability to stimulate NK cell–mediated cytotoxicity. From this screen, we identified five antibodies that bound with high affinity to NK cells and stimulated NK cell–mediated cytotoxicity and interferon-γ (IFN-γ) secretion. We demonstrate that these antibodies can be further developed into bispecific antibodies to redirect NK cell–mediated cytotoxicity toward CD20+ B cell lymphoma cells and HER2+ breast cancer cells. While antibodies to two of the receptors, CD16 and NCR1, have previously been targeted as bispecific antibodies to redirect NK cell–mediated cytotoxicity, we demonstrate that bispecific antibodies targeting NCR3 can also potently activate NK cells. These results show that this screen can be used to directly identify antibodies that can enhance antitumor immune responses. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antibody; Bispecific antibodies; Immunotherapy; Natural killer cells
语种	英语
scopus关键词	antibody; cell surface receptor; epidermal growth factor receptor 2; ERBB2 protein, human; Fc receptor; FCGR3B protein, human; gamma interferon; glycosylphosphatidylinositol anchored protein; rituximab; antibody affinity; antibody dependent cellular cytotoxicity; B cell lymphoma; breast tumor; drug effect; female; gene expression regulation; genetics; human; immunology; metabolism; natural killer cell; physiology; reproducibility; tumor cell line; Antibodies; Antibody Affinity; Antibody-Dependent Cell Cytotoxicity; Breast Neoplasms; Cell Line, Tumor; Female; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; GPI-Linked Proteins; Humans; Interferon-gamma; Killer Cells, Natural; Lymphoma, B-Cell; Receptor, ErbB-2; Receptors, Cell Surface; Receptors, IgG; Reproducibility of Results; Rituximab
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251083
作者单位	Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143-2552, United States; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, United States; Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States; Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, CA 94143, United States; Department of Microbiology and Immunology, University of California and the Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143, United States
推荐引用方式 GB/T 7714	Kang E.,Kadoch C.,Rubenstein J.L.,等. A functional mammalian display screen identifies rare antibodies that stimulate NK cell–mediated cytotoxicity[J],2021,118(31).
APA	Kang E.,Kadoch C.,Rubenstein J.L.,Lanier L.L.,&Wells J.A..(2021).A functional mammalian display screen identifies rare antibodies that stimulate NK cell–mediated cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America,118(31).
MLA	Kang E.,et al."A functional mammalian display screen identifies rare antibodies that stimulate NK cell–mediated cytotoxicity".Proceedings of the National Academy of Sciences of the United States of America 118.31(2021).