An anti-TROP2 monoclonal antibody TrMab-6 exerts antitumor activity in breast cancer mouse xenograft models

TOMOHIRO TANAKA, TOMOKAZU OHISHI, TEIZO ASANO, JUNKO TAKEI, REN NANAMIYA, HIDEKI HOSONO, Masato Sano, HIROYUKI HARADA, MANABU KAWADA, MIKA K. KANEKO, YUKINARI KATO

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Trophoblast cell surface antigen 2 (TROP2), reported to be overexpressed in several types of cancer, is involved in cell proliferation, invasion, metastasis, and poor prognosis of many types of cancer. Previously, a highly sensitive anti-TROP2 monoclonal antibody (clone TrMab-6; mouse IgG2b, κ) was developed using a Cell-Based Immunization and Screening (CBIS) method. TrMab-6 was useful for investigations using flow cytometry, western blot, and immunohistochemistry. The aim of the present study was to investigate whether TrMab-6 possesses in vitro antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) activities or in vivo antitumor activities using mouse xenograft models of TROP2-overexpressed CHO-K1 (CHO/TROP2) and breast cancer cell lines, including MCF7, MDA-MB-231, and MDA-MB-468. In vitro experiments revealed that TrMab-6 strongly induced ADCC and CDC activities against CHO/TROP2 and the three breast cancer cell lines, whereas it did not show those activities against parental CHO-K1 and MCF7/TROP2-knockout cells. Furthermore, in vivo experiments on CHO/TROP2 and MCF7 xenografts revealed that TrMab-6 significantly reduced tumor growth, whereas it did not show antitumor activities against parental CHO-K1 and MCF7/TROP2-knockout xenografts. The findings suggest that TrMab-6 is a promising treatment option for TROP2-expressing breast cancers.

Original languageEnglish
Article number8083
JournalOncology reports
Volume46
Issue number1
DOIs
Publication statusPublished - 2021 Jul

Keywords

  • ADCC
  • Antitumor activity
  • Breast cancer
  • CDC
  • Monoclonal antibody
  • TROP2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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