Institute of Pharmaceutical Innovation, School of Medicine, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, Hubei, China.
State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.
Theranostics. 2023 Mar 5;13(5):1520-1544. doi: 10.7150/thno.80091. eCollection 2023.
Immunotherapy has achieved great success recently and opened a new avenue for anti-tumor treatment. Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) are typical immune checkpoints that transmit coinhibitory signals, muting the host immunity. Monoclonal antibodies that block PD-1/PD-L1 axis have benefited many patients with different tumor diseases. However, the objective response rate is still unsatisfactory. In this review, we summarize three strategies targeting PD-L1 based on different forms of PD-L1 and various regulating mechanisms to enhance the therapeutic effect, including blockade of the interaction between PD-L1 and PD-1, downregulation of PD-L1 expression and degradation of mature PD-L1. Thereinto, we describe a variety of materials have been designed to target PD-L1, including antibodies, nanoparticle, peptide, aptamer, RNA, and small molecule. Additionally, we list the drugs with PD-L1 regulation capacity used in clinical and ongoing studies to explore other alternatives for targeting PD-L1 besides anti-PD-L1 monoclonal antibodies. Moreover, we discuss associated opportunities for cancer combination therapy with other modalities such as chemotherapy, radiotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), as these conventional or emerging modalities are capable of increasing the immune response of tumor cells by altering the tumor microenvironment (TME), and would display synergistic effect. At last, we give a brief summary and outlook regarding the research status and future prospect of immunotherapy.
免疫疗法最近取得了巨大的成功，为抗肿瘤治疗开辟了新途径。程序性细胞死亡 1/程序性细胞死亡配体 1（PD-1/PD-L1）是典型的免疫检查点，它们传递共抑制信号，使宿主免疫沉默。阻断 PD-1/PD-L1 轴的单克隆抗体使许多患有不同肿瘤疾病的患者受益。然而，客观缓解率仍不理想。在这篇综述中，我们总结了三种基于 PD-L1 不同形式和各种调节机制的靶向 PD-L1 的策略，以增强治疗效果，包括阻断 PD-L1 与 PD-1 的相互作用、下调 PD-L1 表达和降解成熟 PD-L1。其中，我们描述了多种已设计用于靶向 PD-L1 的材料，包括抗体、纳米颗粒、肽、适体、RNA 和小分子。此外，我们列出了具有 PD-L1 调节能力的药物在临床和正在进行的研究中，以探索除抗 PD-L1 单克隆抗体以外的其他靶向 PD-L1 的替代方案。此外，我们还讨论了与其他方式（如化疗、放疗、光动力疗法（PDT）和光热疗法（PTT））联合治疗癌症的相关机会，因为这些传统或新兴的方式能够通过改变肿瘤微环境（TME）来增加肿瘤细胞的免疫反应，并显示协同效应。最后，我们对免疫疗法的研究现状和未来前景进行了简要总结和展望。
