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Gastric Cancer

, Volume 22, Issue 5, pp 932–940 | Cite as

GC1118, a novel anti-EGFR antibody, has potent KRAS mutation-independent antitumor activity compared with cetuximab in gastric cancer

  • Ji Eun Park
  • Mei Hua Jin
  • Minkyu Hur
  • Ah-Rong Nam
  • Ju-Hee Bang
  • Jonghwa Won
  • Do-Youn OhEmail author
  • Yung-Jue Bang
Original Article
  • 224 Downloads

Abstract

Background

EGFR overexpression in gastric cancer (GC) has been reported in about 30% of patients. However, the anti-EGFR antibodies cetuximab and panitumumab have failed to improve overall survival of GC patients in combination with cytotoxic chemotherapy compared with chemotherapy alone. GC1118, a novel anti-EGFR antibody with a distinct binding epitope compared with cetuximab or panitumumab, has not been tested in GC.

Methods

GC cell lines, SNU-1, SNU-5, SNU-16, SNU-216, SNU-484, SNU-601, SNU-620, SNU-638, SNU-668, SNU-719, AGS, MKN-45, NCI-N87, and KATO-III, were employed to test the effect of cetuximab or GC1118 alone, and combined with the cytotoxic agent cisplatin or 5-fluorouracil (5-FU). Cells were also treat with or without high-affinity ligands EGF 20 ng/ml or HB-EGF 100 ng/ml.

Results

GC1118 exhibited a more potent growth inhibition effect in the majority of cell lines than cetuximab in MTT assay, regardless of the KRAS mutation status of cell lines. Co-treatment of GC1118 and cisplatin or 5-FU inhibited colony formation and migration to a greater extent, even following EGFR ligand stimulation. Ligand-induced p-AKT and p-ERK upregulation were more potently inhibited by combination treatment with GC1118 and chemotherapeutic agents compared with cetuximab plus chemotherapeutic agents. GC1118 also showed more potent anti-tumor effects compared with cetuximab in a mouse xenograft model.

Conclusion

Taken together, GC1118 alone or in combination with cytotoxic chemotherapeutic agents exerted more potent anti-tumor effects than cetuximab in GC cells, regardless of KRAS status. These findings support the further clinical development of GC1118 for the treatment of GC.

Keywords

EGFR GC1118 Cetuximab Gastric cancer KRAS 

Notes

Acknowledgements

This study was supported by MOGAM Institute for Biomedical Research fund (Grant No. 06-2013-1580 and 06-2014-3250) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number 2016R1D1A1A09918133).

Compliance with ethical standards

Conflict of interest

The authors disclose no potential conflicts of interest.

Ethical approval

All institutional and national guidelines for the care and use of laboratory animals were followed.

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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2019

Authors and Affiliations

  • Ji Eun Park
    • 1
  • Mei Hua Jin
    • 1
  • Minkyu Hur
    • 3
  • Ah-Rong Nam
    • 1
  • Ju-Hee Bang
    • 1
  • Jonghwa Won
    • 3
  • Do-Youn Oh
    • 1
    • 2
    Email author
  • Yung-Jue Bang
    • 1
    • 2
  1. 1.Cancer Research InstituteSeoul National University College of MedicineSeoulSouth Korea
  2. 2.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea
  3. 3.MOGAM Institute for Biomedical ResearchYonginSouth Korea

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