ScholarWorks@중앙대학교

초록

Traditional monoclonal antibodies like trastuzumab encounter limitations when treating HER2-positive breast cancer, particularly in cases that develop resistance. This study introduces a plant-derived anti-HER2 VHH-FcK antibody as a potent alternative for overcoming these limitations. A variety of biophysical techniques, in vitro assays, and in vivo experiments uncovers the antibody's nano-scale binding dynamics with transmembrane HER2 on living cells. Single-molecule force spectroscopy reveals the rapid formation of two robust bonds, exhibiting approximately 50 pN of force resistance and bond lifetimes in the second range. The antibody demonstrates specific affinity to 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 anti-tumor 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.