Department of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63108, USA.
Int J Mol Sci. 2022 Mar 11;23(6):3041. doi: 10.3390/ijms23063041.
Therapeutic antibodies used to treat cancer are effective in patients with advanced-stage disease. For example, antibodies that activate T-lymphocytes improve survival in many cancer subtypes. In addition, antibody-drug conjugates effectively target cytotoxic agents that are specific to cancer. This review discusses radiation-inducible antigens, which are stress-regulated proteins that are over-expressed in cancer. These inducible cell surface proteins become accessible to antibody binding during the cellular response to genotoxic stress. The lead antigens are induced in all histologic subtypes and nearly all advanced-stage cancers, but show little to no expression in normal tissues. Inducible antigens are exploited by using therapeutic antibodies that bind specifically to these stress-regulated proteins. Antibodies that bind to the inducible antigens GRP78 and TIP1 enhance the efficacy of radiotherapy in preclinical cancer models. The conjugation of cytotoxic drugs to the antibodies further improves cancer response. This review focuses on the use of radiotherapy to control the cancer-specific binding of therapeutic antibodies and antibody-drug conjugates.
用于治疗癌症的治疗性抗体在晚期疾病患者中有效。例如，激活 T 淋巴细胞的抗体可提高多种癌症亚型的生存率。此外，抗体药物偶联物可有效靶向针对癌症的细胞毒性药物。本文综述了辐射诱导抗原，即癌症中过度表达的应激调节蛋白。在细胞对遗传毒性应激的反应过程中，这些可诱导的细胞表面蛋白变得可与抗体结合。在所有组织学亚型和几乎所有晚期癌症中都会诱导出主要抗原，但在正常组织中表达很少或没有。通过使用特异性结合这些应激调节蛋白的治疗性抗体来利用可诱导抗原。与诱导抗原 GRP78 和 TIP1 结合的抗体可增强放射治疗在临床前癌症模型中的疗效。将细胞毒性药物与抗体偶联进一步提高了癌症的反应率。本文重点介绍了使用放射疗法来控制治疗性抗体和抗体药物偶联物的癌症特异性结合。
