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:Innate immune cells in chimeric antigen receptor therapy.
Innate immune cells in chimeric antigen receptor therapy.
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嵌合抗原受体(CAR)疗法革新了癌症治疗,CAR-T 细胞治疗血液系统恶性肿瘤的成功尤为突出。但其用于实体瘤仍受多项重大挑战限制,包括细胞因子释放综合征、神经毒性、肿瘤浸润不佳、抗原异质性和制造成本高。因此,替代性免疫效应细胞日益受到关注。自然杀伤(NK)细胞、巨噬细胞、不变型NK T细胞、γδT细胞、树突状细胞和中性粒细胞等先天免疫细胞具有独特优势:移植物抗宿主病风险较低,具有内在的肿瘤归巢和细胞毒能力,并适合制备现货型治疗产品。本综述探讨CAR工程化先天免疫细胞的生物学依据和临床潜力,重点介绍临床前及临床研究的关键发现。最后,我们讨论可能影响下一代实体瘤CAR疗法发展的联合策略和未来方向。
Chimeric antigen receptor (CAR) therapies have revolutionized cancer treatment, particularly with the success of CAR-T cells in hematologic malignancies.
However, their application to solid tumors remains limited by major challenges, including cytokine release syndrome, neurotoxicity, poor tumor infiltration, antigen heterogeneity, and high manufacturing costs. These limitations have prompted growing interest in alternative immune effector cells. Innate immune cells, such as natural killer (NK) cells, macrophages, invariant NK T cells, T cells, dendritic cells, and neutrophils, offer distinct advantages.
They are associated with a lower risk of graft-versus-host disease, possess intrinsic tumor-homing and cytotoxic properties, and are suitable for off-the-shelf therapeutic platforms. This review explores the biological rationale and clinical potential of CAR-engineered innate immune cells, highlighting key findings from preclinical and clinical studies.
Finally, we discuss combinatorial strategies and future directions that could shape the next generation of CAR-based therapies for solid tumors.
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