TY - JOUR
T1 - PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein
AU - Thura, Min
AU - Al-Aidaroos, Abdul Qader
AU - Gupta, Abhishek
AU - Chee, Cheng Ean
AU - Lee, Soo Chin
AU - Hui, Kam Man
AU - Li, Jie
AU - Guan, Yeoh Khay
AU - Yong, Wei Peng
AU - So, Jimmy
AU - Chng, Wee Joo
AU - Ng, Chin Hin
AU - Zhou, Jianbiao
AU - Wang, Ling Zhi
AU - Yuen, John Shyi Peng
AU - Ho, Henry Sun Sien
AU - Yi, Sim Mei
AU - Chiong, Edmund
AU - Choo, Su Pin
AU - Ngeow, Joanne
AU - Ng, Matthew Chau Hsien
AU - Chua, Clarinda
AU - Yeo, Eugene Shen Ann
AU - Tan, Iain Bee Huat
AU - Sng, Joel Xuan En
AU - Tan, Nicholas Yan Zhi
AU - Thiery, Jean Paul
AU - Goh, Boon Cher
AU - Zeng, Qi
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-10127-x
DO - 10.1038/s41467-019-10127-x
M3 - Article
C2 - 31171773
AN - SCOPUS:85066931494
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2484
ER -
