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:CAR-engineered NK cells versus CAR T cells in treatment of glioblastoma; strength and flaws.
CAR-engineered NK cells versus CAR T cells in treatment of glioblastoma; strength and flaws.
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胶质母细胞瘤(GBM)是一种高度侵袭性的原发性脑肿瘤,预后极差。由于GBM治疗选择匮乏,嵌合抗原受体(CAR)工程化T细胞和自然杀伤(NK)细胞疗法可为应对治疗挑战提供替代策略。这些方法通过工程化CAR-T 和NK细胞,使其不依赖主要组织相容性复合体(MHC)分子识别表面抗原,实现癌症特异性免疫治疗。
然而,GBM下调靶抗原,限制CAR-T 细胞疗效。CAR-NK细胞面临类似挑战,但也具有优势:可制备现货型异体产品、无移植物抗宿主病(GVHD)风险,并且CAR特异性之外仍有抗癌活性,可能降低复发或耐药风险。尽管CAR-T 细胞疗法已在临床环境中得到广泛研究,CAR修饰NK细胞治疗GBM目前仍主要处于临床前阶段。本综述讨论NK细胞和CAR-T 细胞疗法治疗GBM的近期进展,包括向NK细胞和T细胞导入CAR的方法、生产挑战,以及支持这些方法疗效的临床前和早期临床研究证据。对CAR工程化NK细胞和CAR-T 细胞进行全面评估,旨在确定GBM的最佳治疗策略,并推动开发针对这一严重疾病的有效免疫疗法。
Glioblastoma (GBM) is a highly aggressive primary brain tumor that carries a grim prognosis. Because of the dearth of treatment options available for treatment of GBM, Chimeric Antigen Receptor (CAR)-engineered T cell and Natural Killer (NK) therapy could provide alternative strategies to address the challenges in GBM treatment. In these approaches, CAR T and NK cells are engineered for cancer-specific immunotherapy by recognizing surface antigens independently of major histocompatibility complex (MHC) molecules.
However, the efficacy of CAR T cells is hindered by GBM's downregulation of its targeted antigens. CAR NK cells face similar challenges, but, in contrast, they offer advantages as off-the-shelf allogeneic products, devoid of graft-versus-host disease (GVHD) risk as well as anti-cancer activity beyond CAR specificity, potentially reducing the risk of relapse or resistance. Despite CAR T cell therapies being extensively studied in clinical settings, the use of CAR-modified NK cells in GBM treatment remains largely in the preclinical stage.
This review aims to discuss recent advancements in NK cell and CAR T cell therapies for GBM, including methods for introducing CARs into both NK cells and T cells, addressing manufacturing challenges, and providing evidence supporting the efficacy of these approaches from preclinical and early-phase clinical studies. The comprehensive evaluation of CAR-engineered NK cells and CAR T cells seeks to identify the optimal therapeutic approach for GBM, contributing to the development of effective immunotherapies for this devastating disease.
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