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journal article·2024-06-25Open access

Plant-Derived Anti-Human Epidermal Growth Factor Receptor 2 Antibody Suppresses Trastuzumab-Resistant Breast Cancer with Enhanced Nanoscale Binding

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

ACS Nano· Volume 18· Issue 25
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Source abstract

Abstract

High Resolution Image Download MS PowerPoint Slide 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.
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Research context

Nanomaterials

OpenAlex topics: Monoclonal and Polyclonal Antibodies Research · Transgenic Plants and Applications · Toxin Mechanisms and Immunotoxins

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

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

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

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

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

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

Funding

National Research Council of Science and Technology · Austrian Science Fund · National Research Foundation of Korea · ??sterreichische Nationalstiftung f??r Forschung, Technologie und Entwicklung · Research Department of the State of Upper Austria · Austrian Federal Ministry of Education, Science and Research and the Ministry of Science and ICT of the Republic of Korea

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