Oya Kazumasa, Shen Larina Tzu-Wei, Maruo Kazushi, Matsusaka Satoshi
Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Department of Clinical Research and Regional Innovation, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8587, Japan.
Biomedicines. 2022 Oct 5;10(10):2483. doi: 10.3390/biomedicines10102483.
The antitumor effect of antibody-drug conjugates (ADC) is the main factor in achieving cures. Although the mechanism of tumor resistance to treatment is multifaceted, tumor-derived extracellular vesicles (T-EVs) have been implicated as contributing to the attenuation of ADC therapeutic efficacy. Thus, strategies to eliminate T-EVs are highly promising for overcoming drug resistance. Here we demonstrate plasma exchange therapy to remove T-EVs, decreasing their amount in vitro by 75%. Although trastuzumab emtansine (T-DM1) treatment alone was effective in our rat tumor model, the combination therapy of T-DM1 and T-EV filtration achieved early tumor shrinkage. Our results indicate that T-EV filtration plus ADC is a promising strategy for overcoming drug resistance.
抗体药物偶联物（ADC）的抗肿瘤作用是实现治愈的主要因素。尽管肿瘤对治疗产生耐药性的机制是多方面的，但肿瘤来源的细胞外囊泡（T-EV）被认为是导致ADC治疗效果减弱的原因之一。因此，消除T-EV的策略对于克服耐药性具有很大的前景。在此，我们展示了血浆置换疗法可去除T-EV，在体外将其数量减少75%。虽然单独使用曲妥珠单抗-美坦新（T-DM1）治疗在我们的大鼠肿瘤模型中有效，但T-DM1与T-EV过滤的联合治疗实现了肿瘤早期缩小。我们的结果表明，T-EV过滤联合ADC是一种有前景的克服耐药性的策略。
