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A Novel Anti-Her2 Bispecific Antibody With Potent Tumor Inhibitory Effects in Vitro and in Vivo Publisher Pubmed



Mohammadi M1 ; Jedditehrani M3 ; Golsazshirazi F1 ; Arjmand M2 ; Bahadori T1 ; Judaki MA1 ; Shiravi F1 ; Zare HA3 ; Haghighat FN3 ; Mobini M1 ; Amiri MM1 ; Shokri F1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
  3. 3. Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran

Source: Frontiers in Immunology Published:2021


Abstract

Overexpression of HER2 has been reported in many types of cancer, making it a perfect candidate for targeted immunotherapy. The combination of two FDA approved monoclonal antibodies (mAbs), trastuzumab and pertuzumab, has more robust anti-tumor activity in patients with HER2-overexpressing breast cancer. We recently produced a new humanized anti-HER2 mAb, hersintuzumab, which recognizes a different epitope than trastuzumab and pertuzumab on HER2. This mAb, in combination with trastuzumab, exhibits more potent anti-tumor activity than each parental mAb alone. Here we have developed a novel bispecific anti-HER2 antibody (BsAb) designated as trasintuzumab, composed of trastuzumab and hersintuzumab, using dual variable domain immunoglobulin (DVD-Ig) technology. Both variable domains of trasintuzumab are fully functional and have similar affinities to the parental mAbs and are also able to bind to natural HER2 on the surface of several HER2-expressing cell lines. Trasintuzumab was found to inhibit the growth of different types of tumor cell lines through suppression of the AKT and ERK signaling pathways as efficiently as the combination of the parental mAbs. It also induced tumor regression as potently as the combination of the two mAbs in nude mice bearing ovarian and gastric cancer xenografts. Our data suggest that trasintuzumab may be a promising BsAb therapeutic candidate for the treatment of HER2-overexpressing cancers. © Copyright © 2021 Mohammadi, Jeddi-Tehrani, Golsaz-Shirazi, Arjmand, Bahadori, Judaki, Shiravi, Zare, Haghighat, Mobini, Amiri and Shokri.
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