Antibody–mimetic drug conjugate is a novel noncovalent conjugate consisting of an antibody-mimetic recognizing a target molecule on the cancer cell surface and low-molecular-weight payloads that kill the cancer cells. In this study, the efficacy of a photo-activating antibody–mimetic drug conjugate targeting HER2-expressing tumors was evaluated in mice, by using the affibody that recognize HER2 (Z_HER2:342) as a target molecule and an axially substituted silicon phthalocyanine (a novel potent photo-activating compound) as a payload. The first treatment with the photo-activating antibody–mimetic drug conjugates reduced the size of all HER2-expressing KPL-4 xenograft tumors macroscopically. However, during the observation period, relapsed tumors gradually appeared in approximately 50% of the animals. To evaluate the efficacy of repeated antibody–mimetic drug conjugate treatment, animals with relapsed tumors were treated again with the same regimen. After the second observation period, the mouse tissues were examined histopathologically. Unexpectedly, all relapsed tumors were eradicated, and all animals were diagnosed with pathological complete remission. After the second treatment, skin wounds healed rapidly, and no significant side effects were observed in other organs, except for occasional microscopic granulomatous tissues beneath the serosa of the liver in a few mice. Repeated treatments seemed to be well tolerated. These results indicate the promising efficacy of the repeated photo-activating antibody–mimetic drug conjugate treatment against HER2-expressing tumors.

中文翻译：

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光激活抗体-模拟药物偶联物治疗复发肿瘤的病理学完全缓解

抗体模拟药物偶联物是一种新型非共价偶联物，由识别癌细胞表面靶分子的抗体模拟物和杀死癌细胞的低分子量有效载荷组成。在这项研究中，通过使用识别 HER2 (Z _{HER2:342 ) 的亲和体，在小鼠中评估了靶向 HER2 表达肿瘤的光激活抗体模拟药物偶联物的功效}) 作为目标分子，轴向取代的硅酞菁（一种新型强效光活化化合物）作为有效载荷。第一次使用光激活抗体模拟药物偶联物进行治疗，从宏观上减小了所有表达 HER2 的 KPL-4 异种移植肿瘤的大小。然而，在观察期间，大约50%的动物逐渐出现复发肿瘤。为了评估重复抗体-模拟药物偶联物治疗的疗效，用相同的方案再次治疗患有复发肿瘤的动物。在第二个观察期后，对小鼠组织进行组织病理学检查。出乎意料的是，所有复发的肿瘤都被根除，所有动物都被诊断为病理完全缓解。第二次治疗后，皮肤伤口迅速愈合，在其他器官中没有观察到明显的副作用，除了在几只小鼠的肝脏浆膜下偶尔出现微小的肉芽肿组织。重复治疗似乎耐受性良好。这些结果表明重复光激活抗体模拟药物偶联物治疗对 HER2 表达肿瘤具有良好的疗效。