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

Dongli Liu1, Gunnar F Kaufmann2, James B Breitmeyer2

  • 1Gynaecological Cancer Research Group, School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW 2052, Australia.

Pharmaceutics
|April 23, 2022
PubMed

Insights

Zilovertamab, an ROR1 antibody, inhibits ovarian and endometrial cancer cell growth. This ROR1-targeting therapy shows potential for treating gynecological cancers, including platinum-resistant types.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The non-canonical Wnt signalling receptor ROR1 is highly expressed in ovarian and endometrial cancers.
  • Silencing ROR1 has previously inhibited cancer cell proliferation and metastasis in vitro.
  • Zilovertamab is an ROR1-targeting monoclonal antibody with proven safety and efficacy in clinical trials.

Purpose of the Study:

  • To evaluate zilovertamab's efficacy alone and with standard therapies in gynecological cancers.
  • To investigate zilovertamab's effect on high-grade serous ovarian cancer (HGSOC) and endometrial cancer (EC) cell lines.
  • To assess zilovertamab's activity in models of platinum resistance and homologous recombination deficiency.

Main Methods:

  • Utilized IncuCyte S3 Live Cell imaging system to monitor cell proliferation.
  • Tested zilovertamab at 25 µg/mL and 50 µg/mL, alone and in combination with cisplatin, paclitaxel, and olaparib.
  • Employed HGSOC (CaOV3, CaOV3CisR, PEO1, PEO4) and EC (Ishikawa, KLE) cell lines.

Main Results:

  • Zilovertamab monotherapy demonstrated significant inhibition of HGSOC and EC cell proliferation in vitro.
  • Anti-proliferative effects were observed across platinum-sensitive, platinum-resistant, and homologous recombination-deficient models.
  • Combination therapy with standard chemotherapies did not generally enhance zilovertamab's anti-proliferative activity.

Conclusions:

  • Zilovertamab exhibits potential as a monotherapy for HGSOC and EC.
  • ROR1-targeting therapies warrant further investigation for gynecological cancer treatment.
  • Zilovertamab's efficacy in platinum-resistant and HR-deficient models suggests broad applicability.
Keywords:
ROR1cirmtuzumabendometrial cancerovarian cancerzilovertamab

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