PRL3-zumab as an Immunotherapy to Inhibit Tumors Expressing PRL3 Oncoprotein

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PRL3-zumab as an Immunotherapy to Inhibit Tumors Expressing PRL3 Oncoprotein
Title:
PRL3-zumab as an Immunotherapy to Inhibit Tumors Expressing PRL3 Oncoprotein
Other Titles:
Nature Communications
Keywords:
Publication Date:
06 June 2019
Citation:
Thura, M., Al-Aidaroos, A.Q., Gupta, A. et al. PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein. Nat Commun 10, 2484 (2019). https://doi.org/10.1038/s41467-019-10127-x
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This research is supported by core funding from Agency for Science Technology and Research, Institute of Molecular and Cell Biology.
Description:
ISSN:
2041-1723
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