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:Chimeric Antigen Receptor Natural Killer T-Cell Therapy for Tumors: Promise and Progress.
然而,该疗法仍面临抗原选择优化、体内扩增与持久性不足、肿瘤异质性及免疫抑制屏障等挑战。未来方向包括推进细胞因子工程与联合治疗。总体而言,CAR-NKT细胞为突破实体瘤治疗困境提供了新思路与新手段,有望成为下一代细胞免疫疗法。
基于嵌合抗原受体工程化的恒定自然杀伤T细胞(chimeric antigen receptor natural killer T [CAR-NKT]细胞)的疗法是一种创新的细胞免疫治疗策略,在实体瘤治疗中较传统CAR-T细胞疗法具有优势。综述:本文综述了CAR-NKT细胞在实体瘤中的研究进展及当前应用。现有研究表明,CAR-NKT细胞能够高效识别肿瘤相关抗原,浸润肿瘤微环境,并通过直接杀伤和细胞因子分泌发挥抗肿瘤作用。与CAR-T疗法相比,CAR-NKT疗法表现出更强的抗肿瘤效力并降低了移植物抗宿主病的发生率。此外,CAR-NKT细胞可通过调节树突状细胞、NK细胞和CD8+ T细胞增强抗肿瘤免疫。针对神经母细胞瘤的早期临床试验及其他实体瘤的临床前试验已显示出良好的安全性和初步疗效,该疗法具有很大的临床转化潜力。
BACKGROUND: Therapy based on chimeric antigen receptor-engineered invariant natural killer T cells (chimeric antigen receptor natural killer T [CAR-NKT] cells) is an innovative cellular immunotherapy strategy that offers advantages over conventional CAR-T cell therapy in the treatment of solid tumors. SUMMARY: This article reviewed the research progress and current application of CAR-NKT cells in solid tumors. Current studies have shown that CAR-NKT cells can efficiently recognize tumor-associated antigens, infiltrate the tumor microenvironment, and exert antitumor effects through direct killing and cytokine secretion. Compared with CAR-T therapy, CAR-NKT therapy exhibits stronger antitumor potency and a reduced incidence of graft-versus-host disease. Furthermore, CAR-NKT cells can enhance antitumor immunity by regulating dendritic cells, NK cells, and CD8+ T cells. Early clinical trials for neuroblastoma and preclinical trials for other solid tumors have shown good safety and preliminary efficacy, and therapies have great potential for clinical translation. KEY MESSAGES: However, this therapy still faces challenges such as optimizing antigen selection, insufficient in vivo expansion and persistence, tumor heterogeneity, and immune suppression barriers. Future directions include advancing cytokine engineering and combination therapies. Collectively, CAR-NKT cells provide new ideas and new means to break through the difficulties in treating solid tumors and hold the promise of becoming the next generation of cellular immunotherapy.
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