决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Nano meets CAR-T: A new era in cancer immunotherapy.
嵌合抗原受体(CAR)-T细胞免疫疗法是癌症个性化治疗中新兴的进展之一,其设计基于对T细胞进行基因修饰以表达嵌合抗原受体(CAR),从而生成CAR-T细胞,特异性靶向癌症组织。
嵌合抗原受体(CAR)T 细胞免疫疗法是癌症个体化治疗领域的新兴进展之一,其设计原理是通过基因修饰使 T 细胞表达 CAR,从而制备能够特异性靶向癌组织的 CAR-T 细胞。尽管免疫疗法具有显著抗肿瘤活性,但受肿瘤耐药、副作用、生产成本高、CAR-T 细胞工程化过程可能产生毒性以及选择性不足等挑战影响,获 FDA 批准并上市的疗法仍然有限。纳米技术为提高药物靶向性和选择性、减少副作用提供了有前景的途径。近期进展显示,纳米材料可用于改进 CAR-T 细胞工程化、递送及体内功能。纳米技术策略包括基于纳米颗粒的基因递送系统、用于调控 CAR 表达的纳米制剂,以及对肿瘤微环境的调节;这些策略在克服当前治疗局限方面显示出显著潜力。因此,目前大量研究正聚焦于将纳米技术整合进 CAR-T 细胞免疫疗法。本综述聚焦 CAR-T 细胞的生物工程、抗肿瘤作用机制、挑战与局限,以及用于补充 CAR-T 免疫疗法的最新纳米技术方案;同时强调纳米技术的转化应用与设计创新,包括精准靶向平台和多功能纳米载体,并指出纳米技术可能有助于提升个体化 CAR-T 癌症免疫疗法的疗效、安全性和临床适用性。
Chimeric antigen receptor (CAR)-T cell immunotherapy is one of the emerging advancements in personalized treatment of cancer, whose design is based on the genetic modification of T cells to express chimeric antigen receptors (CARs) to generate CAR-T cells, specifically targeting cancer tissues. Despite the fact that immunotherapy provides significant antitumor activity, only a limited number of therapies reached the market after their FDA approval because of the accompanying challenges including tumor resistance, side effects, high cost of production, possible toxicities during CAR-T cells engineering, and poor selectivity. Nanotechnology has emerged as a promising approach for improving drug targeting, selectivity and reducing their side effects. In this context, recent advances highlight the innovative integration of nanomaterials for enhancing CAR-T cell engineering, delivery, and in vivo functionality. Nanotechnology-enabled strategies such as nanoparticle-based gene delivery systems, nanoformulations for controlled CAR expression, and tumor microenvironment modulation have demonstrated significant potential in overcoming current therapeutic limitations. Therefore, substantial research efforts are currently focused on integrating this technology in developing CAR-T cell immunotherapy. This review article focuses on CAR-T cell bioengineering, antitumor mechanism of action, challenges and limitations, as well as the latest innovative nanotechnological solutions for complementing CAR-T cell immunotherapy. It also emphasizes the translational applications and design innovations of nanotechnology, including precision targeting platforms and multifunctional nanocarriers, highlighting that nanotechnology may play an important role in advancing the efficacy, safety, and clinical applicability of personalized CAR-T cancer immunotherapy.
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