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ACS Nano, May 19 2024, | https://doi.org/10.1021/acsnano.4c00360 Plant-Derived Anti-Human Epidermal Growth Factor Receptor 2 Antibody Suppresses Trastuzumab-Resistant Breast Cancer with Enhanced Nanoscale Binding

Chanyong Park ¹, Kibum Kim ², Yerin Kim ², Rong Zhu ³, Lisa Hain ³, Hannah Seferovic ³, Min-Hyeok Kim ¹, Hyun Joo Woo ⁴, Hyunju Hwang ², Seung Ho Lee ⁴, Sangmin Kim ⁵, Jeong Eon Lee ⁶, Peter Hinterdorfer ³, Kisung Ko ², Sungsu Park ¹, Yoo Jin Oh ³

¹School of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, Korea.

²Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University, Seoul 06974, Korea.

³Department of Applied Experimental Biophysics, Institute of Biophysics, Johannes Kepler University Linz, 4040 Linz, Austria.

⁴Major of Nano-Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea.

⁵Department of Breast Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

⁶Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Corresponding Authors : Kisung Ko, Sungsu Park, Yoo Jin Oh

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.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-21)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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