Defucosylated Mouse-Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors

Cells. 2021 Dec 20;10(12):3599. doi: 10.3390/cells10123599.

Abstract

The epidermal growth factor receptor (EGFR) contributes to tumor malignancy via gene amplification and protein overexpression. Previously, we developed an anti-human EGFR (hEGFR) monoclonal antibody, namely EMab-134, which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-EGFR monoclonal antibody, namely E134Bf. In vitro analysis revealed that E134Bf highly exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against a canine osteosarcoma cell line (D-17) and a canine fibroblastic cell line (A-72), both of which express endogenous dEGFR. Moreover, in vivo administration of E134Bf significantly suppressed the development of D-17 and A-72 compared with the control dog IgG in mouse xenografts. These results indicate that E134Bf exerts antitumor effects against dEGFR-expressing canine cancers and could be valuable as part of an antibody treatment regimen for dogs.

Keywords: ADCC; CDC; EGFR; antitumor activity; canine osteosarcoma; mouse–dog chimeric antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibody-Dependent Cell Cytotoxicity
  • Antineoplastic Agents / pharmacology*
  • Body Weight / drug effects
  • CHO Cells
  • Complement System Proteins / metabolism
  • Cricetulus
  • Dogs
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Fucose / metabolism*
  • Mice
  • Recombinant Proteins / pharmacology*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Recombinant Proteins
  • Fucose
  • Epidermal Growth Factor
  • Complement System Proteins
  • ErbB Receptors