工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Aptamer based immunotherapy: a potential solid tumor therapeutic.
Aptamer based immunotherapy: a potential solid tumor therapeutic.
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基于适配体的免疫疗法有望成为治疗实体瘤的新希望,通过个性化和特异性的方法进行癌症治疗。适配体是小型合成单链核酸,可能为实体瘤治疗带来范式转变。这些高度选择性的药物应用于细胞免疫治疗、细胞因子调节和免疫检查点抑制。本综述概述了基于适配体技术的最新进展,并特别介绍了涉及 AON-D21 和 AM003 的关键临床试验。适配体在免疫调节和肿瘤靶向方面具有强效活性。
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相关问题而严重受损。本文对此进行了综述,并介绍了新的改进措施,其中一些涉及化学修饰,可大大增强稳定性并延长循环时间;此类修饰的典型例子包括 PEG化、胆固醇偶联和环状核酸的合成。监管方面也至关重要。例如,除了在癌症治疗药物中预防药物相互作用(DDIs)的具体策略外,本文还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展了适配体的应用。为了使基于适配体的药物成为癌症治疗的主要组成部分,未来的研究应更多集中于解决现有问题和扩大其有益用途。
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.
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