Dr. Roffler, Steve R. 's publons link picture


Division Chief
  • 02-2652-3079 (Lab) (Room No: N233)
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  1. Antibody Engineering
  2. Directed Molecular Evolution
  3. Prodrugs

Education and Positions:
  • Ph.D. University of California, Berkeley

Highlight Detail

Bispecific Antibody (HER2 × mPEG) Enhances Anti-Cancer Effects by Precise Targeting and Accumulation of mPEGylated Liposomes

Dr. Roffler, Steve R.
Acta Biomaterialia, May 15, 2020


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 (αmPEG scFv) was fused to the C-terminus of an anti-HER2 (αHER2) antibody to generate a HER2 × mPEG BsAb that retained the original efficacy of a targeted antibody while actively attracting mPEG-liposomes to accumulate at tumor sites. HER2 × mPEG BsAb can simultaneously bind to HER2-high expressing MCF7/HER2 tumor cells and mPEG molecules on mPEG-liposomal doxorubicin (Lipo-Dox). Pre-incubation of HER2 × 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 × 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/neo1 tumors. Importantly, HER2 × 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 × 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.