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Title: | PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein | Authors: | Thura, Min Al-Aidaroos, Abdul Qader Gupta, Abhishek Chee, Cheng Ean Lee, Soo Chin Hui, Kam Man Li, Jie Guan, Yeoh Khay Yong, Wei Peng So, Jimmy Chng, Wee Joo Ng, Chin Hin Zhou, Jianbiao Wang, Ling Zhi Yuen, John Shyi Peng Ho, Henry Sun Sien Yi, Sim Mei Chiong, Edmund Choo, Su Pin Ngeow, Joanne Ng, Matthew Chau Hsien Chua, Clarinda Yeo, Eugene Shen Ann Tan, Iain Bee Huat Sng, Joel Xuan En Tan, Nicholas Yan Zhi Thiery, Jean Paul Goh, Boon Cher Zeng, Qi |
Keywords: | Antibodies Cancer Immunotherapy Science::Medicine |
Issue Date: | 2019 | Source: | Thura, M., Al-Aidaroos, A. Q., Gupta, A., Chee, C. E., Lee, S. C., Hui, K. M., . . . Zeng, Q. (2019). PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein. Nature Communications, 10(1), 2484-. doi:10.1038/s41467-019-10127-x | Series/Report no.: | Nature Communications | Abstract: | Tumor-specific antibody drugs can serve as cancer therapy with minimal side effects. A humanized antibody, PRL3-zumab, specifically binds to an intracellular oncogenic phosphatase PRL3, which is frequently expressed in several cancers. Here we show that PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro. PRL3 antigens are detected on the cell surface and outer exosomal membranes, implying an ‘inside-out’ externalization of PRL3. PRL3-zumab binds to surface PRL3 in a manner consistent with that in classical antibody-dependent cell-mediated cytotoxicity or antibody-dependent cellular phagocytosis tumor elimination pathways, as PRL3-zumab requires an intact Fc region and host FcγII/III receptor engagement to recruit B cells, NK cells and macrophages to PRL3+ tumor microenvironments. PRL3 is overexpressed in 80.6% of 151 fresh-frozen tumor samples across 11 common cancers examined, but not in patient-matched normal tissues, thereby implicating PRL3 as a tumor-associated antigen. Targeting externalized PRL3 antigens with PRL3-zumab may represent a feasible approach for anti-tumor immunotherapy. | URI: | https://hdl.handle.net/10356/79479 http://hdl.handle.net/10220/49728 |
DOI: | 10.1038/s41467-019-10127-x | Schools: | Lee Kong Chian School of Medicine (LKCMedicine) | Rights: | © 2019 The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles |
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PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein.pdf | 4.63 MB | Adobe PDF | View/Open |
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