CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Emerging advances in nanobiomaterials-assisted chimeric antigen receptor (CAR)-macrophages for tumor immunotherapy.
Emerging advances in nanobiomaterials-assisted chimeric antigen receptor (CAR)-macrophages for tumor immunotherapy.
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过继性细胞免疫治疗,尤其是嵌合抗原受体(CAR)-T细胞疗法,在血液系统恶性肿瘤的临床治疗中取得了巨大进展。然而,受限于复杂的肿瘤微环境,T细胞浸润的潜在效率及活化免疫细胞受到限制,因而失败阻止了实体瘤的进展。作为替代,肿瘤相关巨噬细胞(TAMs),作为肿瘤微环境中一个支持性且异质性的细胞群体,被视为潜在的治疗靶点。近年来,CARs通过装备巨噬细胞在治疗恶性肿瘤方面显示出巨大前景。这种新型治疗策略规避了肿瘤微环境的限制,并提供了一种更安全的治疗途径。
同时,纳米生物材料作为基因递送载体,不仅大幅降低了这种新型治疗策略的治疗成本,也为体内CAR-M治疗奠定了基础。在此,我们重点介绍为CAR-M准备的主要策略,强调这些方法的挑战和机遇。首先,在临床和临床前试验中总结了巨噬细胞的常见治疗策略。即,TAM靶向治疗策略:1)抑制单核细胞或巨噬细胞向肿瘤的募集,2)清除TAMs,以及3)将TAMs重编程为抗肿瘤M1表型。其次,综述了CAR-M治疗的当前发展和进展,包括研究者在CAR结构设计、细胞来源和基因递送载体方面的尝试,尤其是纳米生物材料作为病毒载体的替代,同时也总结和讨论了当前CAR-M治疗面临的一些挑战。
最后,展望了基因工程巨噬细胞与纳米技术在肿瘤学中整合的未来领域。
Adoptive cell immunotherapy, especially chimeric antigen receptor (CAR)-T-cells therapy, has made great progress in the clinical treatment of hematological malignancies.
However, restricted by the complex tumor microenvironment, the potential efficiency of T-cell infiltration and activated immune cells are limited, thus failure prevented the progression of the solid tumor. Alternatively, tumor-associated macrophages (TAMs), one sustentacular and heterogeneous cellular population within the tumor microenvironment, are regarded as potential therapeutic targets.
Recently, CARs have shown tremendous promise in treating malignancies by equipping macrophages. This novel therapeutic strategy circumvents the tumor microenvironment's limitations and provides a safer therapeutic approach. Meanwhile, nanobiomaterials as gene delivery carriers not only substantially reduce the treatment cost of this novel therapeutic strategy, but also set the foundation for in vivo CAR-M therapy.
Here, we highlight the major strategies prepared for CAR-M, emphasizing the challenges and opportunities of these approaches. First, the common therapeutic strategies for macrophages are summarized in clinical and preclinical trials. Namely, TAM-targeted therapeutic strategies: 1) Inhibit monocyte or macrophage recruitment into tumors, 2) deplete TAMs, and 3) reprogramme TAMs to antitumor M1 phenotype.
Second, the current development and progress of CAR-M therapy are reviewed, including the researchers' attempts in CAR structure design, cell origin, and gene delivery vectors, especially nanobiomaterials as an alternative to viral vectors, as well as some challenges faced by current CAR-M therapy are also summarized and discussed.
Finally, the field of genetically engineered macrophages integration with nanotechnology for the future in oncology has been prospected.
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