PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein

• Main 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
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2019
• Subjects: Antibodies; Cancer Immunotherapy; Science::Medicine
• Online Access: https://hdl.handle.net/10356/79479; http://hdl.handle.net/10220/49728
• Institution: Nanyang Technological University

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.