Mathavan Sarmilah, Tam Yew Joon, Mustaffa Khairul Mohd Fadzli, Tye Gee Jun
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Minden, Pulau Pinang, Malaysia.
Biogenes Technologies Sdn Bhd, Jalan Maklumat, Universiti Putra Malaysia, Serdang, Malaysia.
Front Immunol. 2025 Feb 17;16:1536569. doi: 10.3389/fimmu.2025.1536569. eCollection 2025.
Aptamer-based immunotherapy can be a new hope for treating solid tumors with personalized and specific approaches toward cancer therapies. Aptamers are small synthetic single-stranded nucleic acids that may bring in a paradigm shift in treating solid tumors. These are highly selective drugs applied in cellular immunotherapy, cytokine modulation, and immune checkpoint suppression. This review provides an overview of the recent advances in aptamer-based technologies with specific key clinical trials involving AON-D21 and AM003. Aptamers are potently active in immune regulation and tumor targeting. However, aptamer stability and bioavailability are seriously compromised by the issues relating to renal clearance and rapid degradation through nucleases. The latter are reviewed here along with novel improvements, some of which involve chemical modifications that greatly enhance stability and prolong the circulation time; exemplary such modifications are PEGylation, cholesterol conjugation, and the synthesis of circular nucleic acids. The regulatory aspect is also crucial. For example, in addition to specific strategies to prevent drug-drug interactions (DDIs) in cancer remediation medications, this paper underscores the need of risk assessment, particularly because of immunogenicity and organ failure. The use of aptamers is expanded by the development of SOMAmers, X-aptamers, and bioinformatics. To make aptamer-based drugs a major part of cancer treatment, future research should concentrate more on resolving existing issues and expanding their beneficial uses.
基于适配体的免疫疗法有望为实体瘤治疗带来新希望,为癌症治疗提供个性化、特异性的方法。适配体是小的合成单链核酸,可能会给实体瘤治疗带来范式转变。它们是应用于细胞免疫疗法、细胞因子调节和免疫检查点抑制的高选择性药物。本综述概述了基于适配体技术的最新进展,以及涉及AON-D21和AM003的具体关键临床试验。适配体在免疫调节和肿瘤靶向方面具有强大活性。然而,适配体的稳定性和生物利用度因肾脏清除和核酸酶快速降解等问题而严重受损。本文将对这些问题以及新的改进方法进行综述,其中一些改进方法涉及化学修饰,可大大提高稳定性并延长循环时间;典型的此类修饰包括聚乙二醇化、胆固醇缀合和环状核酸的合成。监管方面也至关重要。例如,除了癌症治疗药物中预防药物相互作用(DDIs)的具体策略外,本文强调了风险评估的必要性,特别是由于免疫原性和器官衰竭。SOMAmers、X-适配体和生物信息学的发展扩大了适配体的应用。为使基于适配体的药物成为癌症治疗的主要组成部分,未来研究应更多地集中于解决现有问题并扩大其有益用途。