Plant-Derived Anti-Human Epidermal Growth Factor Receptor 2 Antibody Suppresses Trastuzumab-Resistant Breast Cancer with Enhanced Nanoscale Bindingopen access
- Authors
- Park, Chanyong; Kim, Kibum; Kim, Yerin; Zhu, Rong; Hain, Lisa; Seferovic, Hannah; Kim, Min-Hyeok; Woo, Hyun Joo; Hwang, Hyunju; Lee, Seung Ho; Kim, Sangmin; Lee, Jeong Eon; Hinterdorfer, Peter; Ko, Kisung; Park, Sungsu; Oh, Yoo Jin
- Issue Date
- May-2024
- Publisher
- American Chemical Society
- Citation
- ACS Nano
- Journal Title
- ACS Nano
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/74178
- DOI
- 10.1021/acsnano.4c00360
- ISSN
- 1936-0851
1936-086X
- Abstract
- Traditional monoclonal antibodies such as Trastuzumab encounter limitations when treating Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer, particularly in cases that develop resistance. This study introduces plant-derived anti-HER2 variable fragments of camelid heavy chain domain (VHH) fragment crystallizable region (Fc) KEDL(K) antibody as a potent alternative for overcoming these limitations. A variety of biophysical techniques, in vitro assays, and in vivo experiments uncover the antibody’s nanoscale binding dynamics with transmembrane HER2 on living cells. Single-molecule force spectroscopy reveals the rapid formation of two robust bonds, exhibiting approximately 50 pN force resistance and bond lifetimes in the second range. The antibody demonstrates a specific affinity for HER2-positive breast cancer cells, including those that are Trastuzumab-resistant. Moreover, in immune-deficient mice, the plant-derived anti-HER2 VHH-FcK antibody exhibits superior antitumor activity, especially against tumors that are resistant to Trastuzumab. These findings underscore the plant-derived antibody’s potential as an impactful immunotherapeutic strategy for treating Trastuzumab-resistant HER2-positive breast cancer. © 2024 The Authors. Published by American Chemical Society.
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