Therapeutic potential of an anti-HER2 single chain antibody-DM1 conjugates for the treatment of HER2-positive cancer
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… T-SA1 and T-SA2 contained cDNA of an anti-HER2 scFv designed according to amino-acid
sequences of V H and V L regions of trastuzumab with a flexible linker and HSA. cDNA was
synthesized by Genscript Biotechnology Company (Nanjing, China) … |
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Antibody-drug conjugates (ADCs) take the advantage of monoclonal antibodies to selectively deliver highly potent cytotoxic drugs to tumor cells， which have become a powerful measure for cancer treatment in recent years. To develop a more effective therapy for human epidermal growth factor receptor 2 (HER2)-positive cancer， we explored a novel ADCs composed of anti-HER2 scFv-HSA fusion antibodies conjugates with a potent cytotoxic drug DM1. The resulting ADCs， T-SA1-DM1 and T-SA2-DM1 (drug-to-antibody ratio in the range of 3.2-3.5) displayed efficient inhibition in the growth of HER2-positive tumor cell lines and the half-maximal inhibitory concentration on SKBR-3 and SKOV3 cells were both at the nanomolar... More
Antibody-drug conjugates (ADCs) take the advantage of monoclonal antibodies to selectively deliver highly potent cytotoxic drugs to tumor cells， which have become a powerful measure for cancer treatment in recent years. To develop a more effective therapy for human epidermal growth factor receptor 2 (HER2)-positive cancer， we explored a novel ADCs composed of anti-HER2 scFv-HSA fusion antibodies conjugates with a potent cytotoxic drug DM1. The resulting ADCs， T-SA1-DM1 and T-SA2-DM1 (drug-to-antibody ratio in the range of 3.2-3.5) displayed efficient inhibition in the growth of HER2-positive tumor cell lines and the half-maximal inhibitory concentration on SKBR-3 and SKOV3 cells were both at the nanomolar levels . In HER2-positive human ovarian cancer xenograft models， T-SA1-DM1 and T-SA2-DM1 also showed remarkable antitumor activity. Importantly， three out of six mice exhibited complete remission without regrowth in the high-dose group of T-SA1-DM1. On the basis of the analysis of luminescence imaging， anti-HER2 scFv-HSA fusion antibodies， especially T-SA1， showed strong and rapid tumor tissue penetrability and distribution compared with trastuzumab. Collectively， the novel type of ADCs is effective and selective targeting to HER2-positive cancer， and may be a promising antitumor drug candidate for further studies.
