Abdu Amir Mohammed Abker, Liu Yanfei, Abduljabbar Rami, Man Yunqi, Chen Qiwen, Liu Zhenbao
Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.
Pharmaceutics. 2025 Jul 22;17(8):948. doi: 10.3390/pharmaceutics17080948.
Tumor immunotherapy has revolutionized cancer treatment by harnessing the immune system to recognize and eliminate malignant cells, with immune checkpoint inhibitors targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) demonstrating remarkable clinical success. However, challenges such as treatment resistance, immune-related adverse effects, and high costs highlight the need for novel therapeutic approaches. Aptamers, short, single-stranded oligonucleotides with high specificity and affinity for target molecules, have emerged as promising alternatives to conventional antibody-based therapies. This review provides a comprehensive analysis of aptamer-based strategies targeting immune checkpoints, with a particular focus on PD-1/PD-L1 and CTLA-4. We summarize recent advances in aptamer design, including bispecific and multifunctional aptamers, and explore their potential in overcoming immune resistance and improving therapeutic efficacy. Additionally, we discuss strategies to enhance aptamer stability, bioavailability, and tumor penetration through chemical modifications and nanoparticle conjugation. Preclinical and early clinical studies have demonstrated that aptamers can effectively block immune checkpoint pathways, restore T-cell activity, and synergize with other immunotherapeutic agents to achieve superior anti-tumor responses. By systematically reviewing the current research landscape and identifying key challenges, this review aims to provide valuable insights into the future directions of aptamer-based cancer immunotherapy, paving the way for more effective and personalized treatment strategies.
肿瘤免疫疗法通过利用免疫系统识别和消除恶性细胞，彻底改变了癌症治疗方式，靶向程序性死亡受体1（PD-1）、程序性死亡配体1（PD-L1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）的免疫检查点抑制剂已取得显著的临床成功。然而，诸如治疗耐药性、免疫相关不良反应和高成本等挑战凸显了新型治疗方法的必要性。适体是对靶分子具有高特异性和亲和力的短单链寡核苷酸，已成为传统基于抗体疗法的有前景的替代方案。本文综述对靶向免疫检查点的基于适体的策略进行了全面分析，特别关注PD-1/PD-L1和CTLA-4。我们总结了适体设计的最新进展，包括双特异性和多功能适体，并探讨了它们在克服免疫耐药性和提高治疗效果方面的潜力。此外，我们讨论了通过化学修饰和纳米颗粒偶联来提高适体稳定性、生物利用度和肿瘤渗透性的策略。临床前和早期临床研究表明，适体可以有效阻断免疫检查点通路，恢复T细胞活性，并与其他免疫治疗药物协同作用以实现卓越的抗肿瘤反应。通过系统回顾当前的研究状况并确定关键挑战，本文综述旨在为基于适体的癌症免疫疗法的未来方向提供有价值的见解，为更有效和个性化的治疗策略铺平道路。
