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:Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures.
Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures.
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近年来,嵌合抗原受体(CAR)-T细胞疗法已成为最具前景的癌症免疫疗法,通常利用患者的T细胞并通过基因工程改造使其靶向癌细胞。尽管近期CAR-T 细胞疗法的改进在治疗血液系统恶性肿瘤方面取得了显著成功,但肿瘤抗原的异质性以及肿瘤微环境(TME)的免疫抑制特性限制了其在实体瘤中的疗效。尽管在使CAR-T 细胞疗法更有效且副作用最小化以治疗血液系统恶性肿瘤方面已付出巨大努力,但仍需开展更多关于其在临床中用于治疗各种其他类型癌症的研究。CAR-T 细胞疗法的主要关注点是细胞因子释放综合征导致的严重毒性,而其他挑战则与复杂性及免疫抑制性TME、肿瘤抗原异质性、细胞迁移困难、CAR-T 细胞耗竭以及肿瘤部位细胞毒性降低有关。本综述讨论了CAR-T 细胞疗法策略和联合疗法的最新发现,以及它们在不同癌症中的有效性。它还涵盖了正在进行的临床试验;当前关于CAR-T 细胞疗法治疗应用面临的挑战,尤其是针对实体瘤;以及不断发展的治疗策略以改善CAR-T 细胞疗法的治疗应用。
In recent years, chimeric antigen receptor (CAR)-T-cell therapy has emerged as the most promising immunotherapy for cancer that typically uses patients' T cells and genetically engineered them to target cancer cells. Although recent improvements in CAR-T-cell therapy have shown remarkable success for treating hematological malignancies, the heterogeneity in tumor antigens and the immunosuppressive nature of the tumor microenvironment (TME) limits its efficacy in solid tumors. Despite the enormous efforts that have been made to make CAR-T-cell therapy more effective and have minimal side effects for treating hematological malignancies, more research needs to be conducted regarding its use in the clinic for treating various other types of cancer.
The main concern for CAR-T-cell therapy is severe toxicities due to the cytokine release syndrome, whereas the other challenges are associated with complexity and immune-suppressing TME, tumor antigen heterogeneity, the difficulty of cell trafficking, CAR-T-cell exhaustion, and reduced cytotoxicity in the tumor site.
This review discussed the latest discoveries in CAR-T-cell therapy strategies and combination therapies, as well as their effectiveness in different cancers. It also encompasses ongoing clinical trials; current challenges regarding the therapeutic use of CAR-T-cell therapy, especially for solid tumors; and evolving treatment strategies to improve the therapeutic application of CAR-T-cell therapy.
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