Du Shiye, Liu Junzhi, Zhang Youjia, Ge Xiaoguang, Gao Shi, Song Jibin
Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
J Control Release. 2025 Feb 10;378:1061-1079. doi: 10.1016/j.jconrel.2024.12.069. Epub 2025 Jan 4.
The interaction between programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) constitutes a critical immune checkpoint pathway that leads to immune tolerance in cancer cells and impacts antitumor treatment. Monoclonal antibody blockade of the PD-L1 immunoinhibitory pathway has demonstrated significant and lasting clinical antitumor responses. Furthermore, PD-L1 serves as an important biomarker for predicting the effectiveness of immune checkpoint inhibitors (ICIs). To date, numerous studies based on monoclonal antibodies have been carried out to detect the expression levels of PD-L1 and predict the antitumor effectiveness of PD-L1 ICIs. However, due to the deficiencies of monoclonal antibodies, researches of PD-L1 peptides have received increasing attention. PD-L1 peptides present promising candidates due to their advantages, including reduced manufacturing costs, enhanced stability, decreased immunogenicity, faster clearance and improved tumor or organ penetration, thereby offering broad application prospects in cancer immunoimaging and immunotherapy. In this review, we analyze the existing evidence on PD-L1 peptides in cancer immunoimaging and immunotherapy. First, the design techniques of different types of PD-L1 targeting peptides and their strengths and weaknesses are briefly introduced. Second, the recent advancements in immunoimaging and the development trends in immunotherapy are summarized. Finally, the existing challenges and future directions in this field are comprehensively deliberated.
程序性死亡蛋白1(PD-1)与程序性死亡配体1(PD-L1)之间的相互作用构成了一条关键的免疫检查点通路,该通路导致癌细胞产生免疫耐受并影响抗肿瘤治疗。对PD-L1免疫抑制通路的单克隆抗体阻断已显示出显著且持久的临床抗肿瘤反应。此外,PD-L1作为预测免疫检查点抑制剂(ICI)疗效的重要生物标志物。迄今为止,已经开展了大量基于单克隆抗体的研究来检测PD-L1的表达水平并预测PD-L1 ICI的抗肿瘤疗效。然而,由于单克隆抗体的缺陷,PD-L1肽的研究受到越来越多的关注。PD-L1肽因其具有降低制造成本、增强稳定性、降低免疫原性、更快清除以及改善肿瘤或器官穿透性等优势而成为有前景的候选物,从而在癌症免疫成像和免疫治疗中具有广阔的应用前景。在本综述中,我们分析了关于PD-L1肽在癌症免疫成像和免疫治疗方面的现有证据。首先,简要介绍了不同类型的靶向PD-L1肽的设计技术及其优缺点。其次,总结了免疫成像的最新进展和免疫治疗的发展趋势。最后,全面探讨了该领域目前存在的挑战和未来方向。