Defucosylated mousedog chimeric antiHER2 monoclonal antibody exerts antitumor activities in mouse xenograft models of canine tumors.
Oncol Rep
; 48(3)2022 Sep.
Article
in En
| MEDLINE
| ID: mdl-35856438
Human epidermal growth factor receptor 2 (HER2) overexpression has been reported in various types of cancer, including breast, gastric, lung, colorectal and pancreatic cancer. A humanized antiHER2 monoclonal antibody (mAb), trastuzumab, has been shown to improve survival of patients in HER2positive breast and gastric cancer. An antiHER2 mAb, H2Mab77 (mouse IgG1, kappa) was previously developed. In the present study, a defucosylated version of mousedog chimeric antiHER2 mAb (H77Bf) was generated. H77Bf possesses a high bindingaffinity [a dissociation constant (KD): 7.5x1010 M, as determined by flow cytometric analysis] for dog HER2overexpressed CHOK1 (CHO/dHER2) cells. H77Bf highly exerted antibodydependent cellular cytotoxicity (ADCC) and complementdependent cytotoxicity (CDC) for CHO/dHER2 cells by canine mononuclear cells and complement, respectively. Moreover, administration of H77Bf significantly suppressed the development of CHO/dHER2 xenograft tumor in mice compared with the control dog IgG. H77Bf also possesses a high bindingaffinity (KD: 7.2x1010 M) for a canine mammary gland tumor cell line (SNP), and showed high ADCC and CDC activities for SNP cells. Intraperitoneal administration of H77Bf in mouse xenograft models of SNP significantly suppressed the development of SNP xenograft tumors compared with the control dog IgG. These results indicated that H77Bf exerts antitumor activities against dHER2positive canine cancers, and could be valuable treatment regimen for canine cancers.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antibodies, Monoclonal
/
Antineoplastic Agents
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2022
Document type:
Article
Affiliation country:
Japan
Country of publication:
Greece