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Novel Anti-FOLR1 Antibody–Drug Conjugate MORAb-202 in Breast Cancer and Non-Small Cell Lung Cancer Cells

Authors
  • Matsunaga, Yuki1
  • Yamaoka, Toshimitsu2
  • Ohba, Motoi2
  • Miura, Sakiko3
  • Masuda, Hiroko1
  • Sangai, Takafumi
  • Takimoto, Masafumi3
  • Nakamura, Seigo1
  • Tsurutani, Junji2
  • 1 (S.N.)
  • 2 (J.T.)
  • 3 (M.T.)
Type
Published Article
Journal
Antibodies
Publisher
MDPI
Publication Date
Feb 01, 2021
Volume
10
Issue
1
Identifiers
DOI: 10.3390/antib10010006
PMID: 33535554
PMCID: PMC7930947
Source
PubMed Central
Keywords
License
Green

Abstract

Antibody–drug conjugates (ADCs), which are currently being developed, may become promising cancer therapeutics. Folate receptor α (FOLR1), a glycosylphosphatidylinositol-anchored membrane protein, is an attractive target of ADCs, as it is largely absent from normal tissues but is overexpressed in malignant tumors of epithelial origin, including ovarian, lung, and breast cancer. In this study, we tested the effects of novel anti-FOLR1 antibody–eribulin conjugate MORAb-202 in breast cancer and non-small cell lung cancer (NSCLC) cell lines. FOLR1 expression, cell proliferation, bystander killing effects, and apoptosis were evaluated in seven breast cancer and nine NSCLC cell lines treated with MORAb-202. Tumor growth and FOLR1 expression were assessed in T47D and MCF7 orthotopic xenograft mouse models after a single intravenous administration of MORAb-202 (5 mg/kg). MORAb-202 was associated with inhibited cell proliferation, with specific selectivity toward FOLR1-expressing breast cancer cell lines. Eribulin, the payload of MORAb-202, was unleashed in HCC1954 cells, diffused into intercellular spaces, and then killed the non-FOLR1-expressing MCF7 cells in co-culture systems. In orthotopic xenograft mouse models, FOLR1-expressing T47D tumors and non-FOLR1-expressing MCF7 tumors were suppressed upon MORAb-202 administration. The novel anti-FOLR1 antibody–eribulin conjugate MORAb-202 has potential antitumor effects in breast cancer.

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