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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(02): e113-e120
DOI: 10.1055/s-0042-1749334
Original Article

Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the Internalization

Hui-Fang Zong
1   Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China
,
Bao-Hong Zhang
1   Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China
,
Jian-Wei Zhu
1   Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China
2   Jecho Institute Co., Ltd., Shanghai, People's Republic of China
› Author Affiliations Funding This work was supported by the National Natural Science Foundation of China (Grant No. 81773621 and 82073751) and Shanghai Science and Technology Commission project (Grant No. 20S11904900).
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Abstract

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. The bispecific targeting could improve the specificity, affinity, and internalization of the ADC molecules. Prolactin preceptor (PRLR) and HER2 have crosstalk signaling in breast cancer, and PRLR undergoes a rapid internalization compared with HER2. To improve the efficacy of HER2 ADCs with enhancing the target specificity and internalization, we constructed a PRLR/HER2-targeting bispecific ADC (BsADC). We evaluated the characterization of PRLR × HER2 BsADC from the affinity and internalization, and further assessed its in vitro cytotoxicity in human breast-cancer cell lines (BT474, T47D, and MDA-MB-231) using Cell Count Kit-8 analysis. Our data demonstrated that PRLR × HER2 BsADC kept the affinity to two targeting antigens after conjugating drugs and exhibited higher internalization efficiency in comparison to HER2 ADC. Furthermore, PRLR × HER2 BsADC demonstrated to have superior antitumor activity in human breast cancer in vitro. In conclusion, our findings indicate that it is feasible through increasing the internalization of target antibody to enhance the antitumor activity and therapeutic potential that could be further evaluated in in vivo animal model.

Keywords

bispecific ADC - PRLR - HER2 - internalization - antitumor

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.




Publication History

Received: 16 February 2022

Accepted: 15 April 2022

Article published online:
04 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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