Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/79479
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: http://dx.doi.org/10.1038/s41467-019-10127-x
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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