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:Natural killer T cells and other innate-like T lymphocytes as emerging platforms for allogeneic cancer cell therapy.
Natural killer T cells and other innate-like T lymphocytes as emerging platforms for allogeneic cancer cell therapy.
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表达嵌合抗原受体(CAR)的T细胞已在血液系统恶性肿瘤患者中取得重大临床成功。然而,这些治疗对实体癌仍基本无效,并且需要在自体环境下制造,耗费大量时间和资源。开发可作为癌症免疫治疗药物的替代性免疫效应细胞,使其能够用于异体环境,对于细胞治疗的进步至关重要。与T细胞不同,Vα24不变自然杀伤T细胞(NKT)不具有同种异体反应性,因此可以从异体供者中生成,用于快速输注给众多患者,而没有移植物抗宿主病的风险。
此外,NKT细胞相较于T细胞产品具有固有优势,包括能够迁移至肿瘤组织、靶向肿瘤相关巨噬细胞、反式激活NK细胞以及交叉致敏肿瘤特异性CD8 T细胞。未修饰的NKT细胞(特异性识别某些类型肿瘤表达的CD1d结合糖脂抗原)和CAR重定向NKT细胞均正在被开发为下一代异体细胞治疗产品。在这篇综述中,我们描述了关于NKT细胞和其他类型先天样T细胞生物学的研究,并总结了未修饰和CAR重定向NKT细胞的临床经验,包括近期关于异体NKT细胞的中期报告。
T cells expressing chimeric antigen receptors (CARs) have achieved major clinical success in patients with hematologic malignancies.
However, these treatments remain largely ineffective for solid cancers and require significant time and resources to be manufactured in an autologous setting. Developing alternative immune effector cells as cancer immunotherapy agents that can be employed in allogeneic settings is crucial for the advancement of cell therapy. Unlike T cells, Vα24-invariant natural killer T cells (NKTs) are not alloreactive and can therefore be generated from allogeneic donors for rapid infusion into numerous patients without the risk of graft-versus-host disease.
Additionally, NKT cells demonstrate inherent advantages over T-cell products, including the ability to traffic to tumor tissues, target tumor-associated macrophages, transactivate NK cells, and cross-prime tumor-specific CD8 T cells.
Both unmodified NKTs, which specifically recognize CD1d-bound glycolipid antigens expressed by certain types of tumors, and CAR-redirected NKTs are being developed as the next generation of allogeneic cell therapy products. In this review, we describe studies on the biology of NKTs and other types of innate-like T cells and summarize the clinical experiences of unmodified and CAR-redirected NKTs, including recent interim reports on allogeneic NKTs.
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