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 vitro. 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.