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.
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，该方法通常利用患者自身的T细胞，通过基因工程改造使其靶向癌细胞。尽管CAR-T细胞疗法的最新进展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。尽管已投入巨大努力以提升CAR-T细胞疗法对血液系统恶性肿瘤的疗效并减少副作用，但针对其在临床中治疗其他多种癌症的应用仍需进一步研究。CAR-T细胞疗法的主要问题在于细胞因子释放综合征引发的严重毒性反应，其他挑战则涉及肿瘤微环境的复杂性与免疫抑制特性、肿瘤抗原异质性、细胞归巢困难、CAR-T细胞耗竭以及肿瘤部位细胞毒性减弱等方面。本综述探讨了CAR-T细胞疗法策略及联合疗法的最新研究成果及其在不同癌症中的疗效，同时涵盖了正在进行的临床试验、当前CAR-T细胞疗法（尤其是针对实体瘤）临床应用面临的挑战，以及为提升该疗法治疗效果而不断发展的治疗策略。
Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures
肿瘤(癌症)患者之家