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A bispecific anti-ErbB2 antibody potently induces ErbB2 internalization and suppresses ErbB2-overexpressing tumor growth.
- Source :
-
Biochemical & Biophysical Research Communications . Sep2016, Vol. 477 Issue 4, p755-760. 6p. - Publication Year :
- 2016
-
Abstract
- The anti-ErbB2 humanized antibody trastuzumab was approved for ErbB2-positive metastatic gastric and gastro-esophageal junction cancer in 2010. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Down-regulation of surface receptors induced by monoclonal antibody (mAb) contributes to its antitumor efficacy. Previous studies have demonstrated that if two anti-ErbB2 mAbs did not compete with each other for binding to ErbB2, the combination of them can enhance ErbB2 internalization. In the present study, we investigated ErbB2 internalization-inducing ability of non-competitive anti-ErbB2 mAb combinations and surprisingly found that most of the mAb combinations tested did not down-regulate ErbB2. Only 4 of 18 non-competitive mAb pairs efficiently induced ErbB2 internalization. Interestingly, although the non-competitive anti-ErbB2 mAbs trastuzumab and pertuzumab, either alone or in combination, were ineffective at inducing ErbB2 internalization, TP L , a bispecific antibody engineered from trastuzumab and pertuzumab, potently down-regulated the ErbB2 molecule. Importantly, TP L exhibited a far greater antitumor effect on ErbB2-overexpressing gastric cancer cell line than trastuzumab plus pertuzumab, suggesting that it may be a promising agent for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 477
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 117007321
- Full Text :
- https://doi.org/10.1016/j.bbrc.2016.06.131