The Anti-ROR1 Monoclonal Antibody Zilovertamab Inhibits the Proliferation of Ovarian and Endometrial Cancer Cells

Liu, D; Kaufmann, GF; Breitmeyer, JB; Dickson, K-A; Marsh, DJ; Ford, CE

The Anti-ROR1 Monoclonal Antibody Zilovertamab Inhibits the Proliferation of Ovarian and Endometrial Cancer Cells

Liu, D Kaufmann, GF Breitmeyer, JB Dickson, K-A Marsh, DJ Ford, CE

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Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: Pharmaceutics, 2022, 14, (4), pp. 837
Issue Date:: 2022-04-11

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Field	Value	Language
dc.contributor.author	Liu, D
dc.contributor.author	Kaufmann, GF
dc.contributor.author	Breitmeyer, JB
dc.contributor.author	Dickson, K-A
dc.contributor.author	Marsh, DJ
dc.contributor.author	Ford, CE
dc.date.accessioned	2022-04-19T06:41:42Z
dc.date.available	2022-04-19T06:41:42Z
dc.date.issued	2022-04-11
dc.identifier.citation	Pharmaceutics, 2022, 14, (4), pp. 837
dc.identifier.issn	1999-4923
dc.identifier.issn	1999-4923
dc.identifier.uri	http://hdl.handle.net/10453/156466
dc.description.abstract	<jats:p>The non-canonical Wnt signalling receptor ROR1 is aberrantly expressed in numerous cancers, including ovarian and endometrial cancer. We previously reported that silencing ROR1 could inhibit the proliferation and metastatic potential of ovarian and endometrial cancer cells in vitro. Zilovertamab is an ROR1-targeting humanised monoclonal antibody, with demonstrated safety and efficacy in clinical trials of several ROR1-related malignancies. The aim of this study was to investigate the potential of zilovertamab alone, or in combination with commonly utilised gynaecological cancer therapies (cisplatin, paclitaxel and the PARP inhibitor—Olaparib) on high-grade serous ovarian cancer (HGSOC), including models of platinum resistance and homologous recombination deficiency (CaOV3, CaOV3CisR, PEO1 and PEO4) and endometrial cancer (EC) cell lines (Ishikawa and KLE). The effect of zilovertamab (at 25 µg/mL or 50 µg/mL) +/− agents was investigated using the IncuCyte S3 Live Cell imaging system. Zilovertamab alone inhibited the proliferation of HGSOC and EC cells in vitro, including in models of platinum resistance and homologous recombination deficiency. In general, the addition of commonly used chemotherapies to a fixed dose of zilovertamab did not enhance the observed anti-proliferative activity. This study supports the potential of zilovertamab, or other ROR1-targeting therapies, for treating women with HGSOC and EC.</jats:p>
dc.language	en
dc.publisher	MDPI AG
dc.relation.ispartof	Pharmaceutics
dc.relation.isbasedon	10.3390/pharmaceutics14040837
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1115 Pharmacology and Pharmaceutical Sciences
dc.title	The Anti-ROR1 Monoclonal Antibody Zilovertamab Inhibits the Proliferation of Ovarian and Endometrial Cancer Cells
dc.type	Journal Article
utslib.citation.volume	14
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-19T06:41:40Z
pubs.issue	4
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	4

Abstract:

The non-canonical Wnt signalling receptor ROR1 is aberrantly expressed in numerous cancers, including ovarian and endometrial cancer. We previously reported that silencing ROR1 could inhibit the proliferation and metastatic potential of ovarian and endometrial cancer cells in vitro. Zilovertamab is an ROR1-targeting humanised monoclonal antibody, with demonstrated safety and efficacy in clinical trials of several ROR1-related malignancies. The aim of this study was to investigate the potential of zilovertamab alone, or in combination with commonly utilised gynaecological cancer therapies (cisplatin, paclitaxel and the PARP inhibitor—Olaparib) on high-grade serous ovarian cancer (HGSOC), including models of platinum resistance and homologous recombination deficiency (CaOV3, CaOV3CisR, PEO1 and PEO4) and endometrial cancer (EC) cell lines (Ishikawa and KLE). The effect of zilovertamab (at 25 µg/mL or 50 µg/mL) +/− agents was investigated using the IncuCyte S3 Live Cell imaging system. Zilovertamab alone inhibited the proliferation of HGSOC and EC cells in vitro, including in models of platinum resistance and homologous recombination deficiency. In general, the addition of commonly used chemotherapies to a fixed dose of zilovertamab did not enhance the observed anti-proliferative activity. This study supports the potential of zilovertamab, or other ROR1-targeting therapies, for treating women with HGSOC and EC.

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http://hdl.handle.net/10453/156466