標題: | Bispecific antibody (HER2 x mPEG) enhances anti-cancer effects by precise targeting and accumulation of mPEGylated liposomes |
作者: | Chen, I-Ju Cheng, Yi-An Ho, Kai-Wen Lin, Wen-Wei Cheng, Kai-Wen Lu, Yun-Chi Hsieh, Yuan-Chin Huang, Chien-Chiao Chuang, Chih-Hung Chen, Fang-Ming Su, Yu-Cheng Roffler, Steve R. Cheng, Tian-Lu 生物科技學系 Department of Biological Science and Technology |
關鍵字: | Bispecific antibody;mPEGylated liposomal doxorubicin;HER2;Methoxy poly (ethylene glycol);Combination therapy;Targeted therapy |
公開日期: | 15-七月-2020 |
摘要: | Targeted antibodies and methoxy-PEGylated nanocarriers have gradually become a mainstream of cancer therapy. To increase the anti-cancer effects of targeted antibodies combined with mPEGylated liposomes (mPEG-liposomes), we describe a bispecific antibody in which an anti-methoxy-polyethylene glycol scFv (alpha mPEG scFv) was fused to the C-terminus of an anti-HER2 (alpha HER2) antibody to generate a HER2 x mPEG BsAb that retained the original efficacy of a targeted antibody while actively attracting mPEG-liposomes to accumulate at tumor sites. HER2 xmPEG BsAb can simultaneously bind to HER2high expressing MCF7/HER2 tumor cells and mPEG molecules on mPEG-liposomal doxorubicin (Lipo-Dox). Pre-incubation of HER2 x mPEG BsAb with cells increased the endocytosis of Lipo-DiD and enhanced the cytotoxicity of Lipo-Dox to MCF7/HER2 tumor cells. Furthermore, pre-treatment of HER2 x mPEG BsAb enhanced the tumor accumulation and retention of Lipo-DiR 2.2-fold in HER2-high expressing MCF7/HER2 tumors as compared to HER2-low expressing MCF7/neol tumors. Importantly, HER2 x mPEG BsAb plus Lipo-Dox significantly suppressed tumor growth as compared to control BsAb plus Lipo-Dox in MCF7/HER2 tumor-bearing mice. These results indicate that HER2 x mPEG BsAb can enhance tumor accumulation of mPEG-liposomes to improve the therapeutic efficacy of combination treatment. Anti-mPEG scFv can be fused to any kind of targeted antibody to generate BsAbs to actively attract mPEG-drugs and improve anti-cancer efficacy. Statement of Significance Antibody targeted therapy and PEGylated drugs have gradually become the mainstream of cancer therapy. To enhance the anti-cancer effects of targeted antibodies combined with PEGylated drugs is very important. To this aim, we fused an anti-PEG scFv to the C-terminal of HER2 targeted antibodies to generate a HER2xmPEG bispecific antibody (BsAb) to retain the original efficacy of targeted antibody whilst actively attract mPEG-liposomal drugs to accumulate at tumor sites. The present study demonstrates pretreatment of HER2xmPEG BsAb can enhance tumor accumulation of mPEG-liposomal drugs to improve the therapeutic efficacy of combination treatment. Anti-mPEG scFv can be fused to any kind of targeted antibody to generate BsAbs to actively attract mPEG-drugs and improve anti-cancer efficacy. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. |
URI: | http://dx.doi.org/10.1016/j.actbio.2020.04.029 http://hdl.handle.net/11536/154985 |
ISSN: | 1742-7061 |
DOI: | 10.1016/j.actbio.2020.04.029 |
期刊: | ACTA BIOMATERIALIA |
Volume: | 111 |
起始頁: | 386 |
結束頁: | 397 |
顯示於類別: | 期刊論文 |