Therapeutic antibodies are instrumental in improving the treatment outcome for certain disease conditions. However, to enhance their efficacy and specificity, many efforts are continuously made. One of the approaches that are increasingly explored in this field are pH-responsive antibodies capable of binding target antigens in a pH-dependent manner. We reviewed suitability and examples of these antibodies that are functionally modulated by the tumor microenvironment. Provided in this review is an update about antigens targeted by pH-responsive, sweeping, and recycling antibodies. Applicability of the pH-responsive antibodies in the engineering of chimeric antigen receptor T-cells (CAR-T) and in improving drug delivery to the brain by the enhanced crossing of the blood–brain barrier is also discussed. The pH-responsive antibodies possess strong treatment potential. They emerge as next-generation programmable engineered biologic drugs that are active only within the targeted biological space. Thus, they are valuable in targeting acidified tumor microenvironment because of improved spatial persistence and reduced on-target off-tumor toxicities. We predict that the programmable pH-dependent antibodies become powerful tools in therapies of cancer.

中文翻译：

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用于治疗应用的 pH 响应性抗体

治疗性抗体有助于改善某些疾病的治疗结果。然而，为了提高其功效和特异性，人们不断做出许多努力。该领域越来越多地探索的方法之一是能够以 pH 依赖性方式结合靶抗原的 pH 响应性抗体。我们回顾了这些受肿瘤微环境功能调节的抗体的适用性和示例。本综述提供了有关 pH 响应型、清除型和回收型抗体靶向抗原的最新信息。还讨论了 pH 响应抗体在嵌合抗原受体 T 细胞 (CAR-T) 工程中的适用性以及通过增强穿过血脑屏障来改善药物向大脑的输送。pH响应性抗体具有强大的治疗潜力。它们作为下一代可编程工程生物药物出现，仅在目标生物空间内发挥作用。因此，它们在靶向酸化肿瘤微环境方面非常有价值，因为它们改善了空间持久性并减少了脱靶肿瘤毒性。我们预测可编程 pH 依赖性抗体将成为癌症治疗的强大工具。