| Updated in 6/25/2019 2:28:48 PM |
Viewed: 279 times |
(Journal Article) |
Nature communications 10 (1): 2484 (2019)
PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein.
Min Thura
,
Abdul Qader Al-Aidaroos
,
Abhishek Gupta
,
Cheng Ean Chee
,
Soo Chin Lee
,
Kam Man Hui
,
Jie Li
,
Yeoh Khay Guan
,
Wei Peng Yong
,
Jimmy So
,
Wee Joo Chng
,
Chin Hin Ng
,
Jianbiao Zhou
,
Ling Zhi Wang
,
John Shyi Peng Yuen
,
Henry Sun Sien Ho
,
Sim Mei Yi
,
Edmund Chiong
,
Su Pin Choo
,
Joanne Ngeow
,
Matthew Chau Hsien Ng
,
Clarinda Chua
,
Eugene Shen Ann Yeo
,
Iain Bee Huat Tan
,
Joel Xuan En Sng
,
Nicholas Yan Zhi Tan
,
Jean Paul Thiery
,
Boon Cher Goh
,
Qi Zeng
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.