气候变化领域集成服务门户(CCPortal): Homogeneous antibody and CAR-T cells with improved effector functions targeting SSEA-4 glycan on pancreatic cancer

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DOI	10.1073/pnas.2114774118
	Homogeneous antibody and CAR-T cells with improved effector functions targeting SSEA-4 glycan on pancreatic cancer
	Lin C.-W.; Wang Y.-J.; Lai T.-Y.; Hsu T.-L.; Han S.-Y.; Wu H.-C.; Shen C.-N.; Dang V.; Chen M.-W.; Chen L.-B.; Wong C.-H.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:50
英文摘要	Pancreatic cancer is usually asymptomatic in the early stages; the 5-y survival rate is around 9%; and there is a lack of effective treatment. Here we show that SSEA-4 is more expressed in all pancreatic cancer cell lines examined but not detectable in normal pancreatic cells; and high expression of SSEA-4 or the key enzymes B3GALT5 + ST3GAL2 associated with SSEA-4 biosynthesis significantly lowers the overall survival rate. To evaluate potential new treatments for pancreatic cancer, homogeneous antibodies with a well-defined Fc glycan for optimal effector functions and CAR-T cells with scFv construct designed to target SSEA-4 were shown highly effective against pancreatic cancer in vitro and in vivo. This was further supported by the finding that a subpopulation of natural killer (NK) cells isolated by the homogeneous antibody exhibited enhancement in cancer-cell killing activity compared to the unseparated NK cells. These results indicate that targeting SSEA-4 by homologous antibodies or CAR-T strategies can effectively inhibit cancer growth, suggesting SSEA-4 as a potential immunotherapy target for treating pancreatic disease. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CAR-T; Homogeneous antibody; Pancreatic cancer; SSEA-4 expression
语种	英语
scopus关键词	antibody; glycan; stage specific embryo antigen 4; antibody; stage specific embryo antigen; stage-specific embryonic antigen-4; animal experiment; animal tissue; antigen expression; Article; biosynthesis; cell killing; cell subpopulation; controlled study; correlational study; in vitro study; in vivo study; mouse; natural killer cell; nonhuman; overall survival; pancreas cancer; pancreas cell; protein targeting; survival rate; adoptive immunotherapy; animal; biological therapy; drug screening; gene expression regulation; human; immunology; immunotherapy; nude mouse; pancreas tumor; tumor cell line; Animals; Antibodies; Cell Line, Tumor; Cell- and Tissue-Based Therapy; Gene Expression Regulation; Humans; Immunotherapy; Immunotherapy, Adoptive; Mice; Mice, Nude; Pancreatic Neoplasms; Stage-Specific Embryonic Antigens; Xenograft Model Antitumor Assays
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/250937
作者单位	Department of Chemistry, The Scripps Research Institute, San diego, CA 92037, United States; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei, 10617, Taiwan; Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan; Department of Cell Biology, CHO Pharma USA, Inc., Woburn, MA 01801, United States; Department of Pathology, Harvard Medical School, Boston, MA 02115, United States
推荐引用方式 GB/T 7714	Lin C.-W.,Wang Y.-J.,Lai T.-Y.,et al. Homogeneous antibody and CAR-T cells with improved effector functions targeting SSEA-4 glycan on pancreatic cancer[J],2021,118(50).
APA	Lin C.-W..,Wang Y.-J..,Lai T.-Y..,Hsu T.-L..,Han S.-Y..,...&Wong C.-H..(2021).Homogeneous antibody and CAR-T cells with improved effector functions targeting SSEA-4 glycan on pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America,118(50).
MLA	Lin C.-W.,et al."Homogeneous antibody and CAR-T cells with improved effector functions targeting SSEA-4 glycan on pancreatic cancer".Proceedings of the National Academy of Sciences of the United States of America 118.50(2021).