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This galley proof is being listed electronically before publishing the final manuscript (It's not final version).

A chemical conjugate between HER2-targeting antibody fragment and Pseudomonas exotoxin A fragment demonstrates cytotoxic effects on HER2-expressing breast cancer cells
Sunju Lee1, Sangsu Park1, Minh Tan Nguyen1,2, Eunyoung Lee1, Julee Kim1, Sangki Baek1, Chong Jai Kim3, Yeon Jin Jang1, Han Choe1,*
1Physiology, Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea,
2Biotechnology, Faculty of Biotechnology, Ho Chi Minh City Open University, 97 Vo Van Tan Street, District 3, Ho Chi Minh City, Vietnam,
3Pathology, Asan-Minnesota Institute for Innovating Transplantation, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea
Conventionally, immunotoxins have been produced as a single polypeptide from fused genes of an antibody fragment and a toxin. In this study, we adopted a unique approach of chemical conjugation of a toxin protein and an antibody fragment. The two genes were separately expressed in Escherichia coli and purified to high levels of purity. The two purified proteins were conjugated using a chemical linker. The advantage of this approach is its ability to overcome the problem of low recombinant immunotoxin production observed in some immunotoxins. Another advantage is that various combinations of immunotoxins can be prepared with fewer efforts, because the chemical conjugation of components is relatively simpler than the processes involved in cloning, expression, and purification of multiple immunotoxins. As a proof of concept, the scFv of trastuzumab and the PE24 fragment of Pseudomonas exotoxin A were separately produced using E. coli and then chemically crosslinked. The new immunotoxin was tested on four breast cancer cell lines variably expressing HER2. The chemically crosslinked immunotoxin exhibited cytotoxicity in proportion to the expression level of HER2. In conclusion, the present study revealed an alternative method of generating an immunotoxin that could effectively reduce the viability of HER2-expressing breast cancer cells. These results suggest the effectiveness of this method of immunotoxin crosslinking as a suitable alternative for producing immunotoxins.
Abstract, Accepted Manuscript(in press) [Submitted on November 5, 2018, Accepted on November 28, 2018]
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