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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Chimeric antigen receptor-based cellular therapy for T-cell malignancies.
Chimeric antigen receptor-based cellular therapy for T-cell malignancies.
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嵌合抗原受体(CAR)T细胞疗法利用合成生物学技术对T细胞进行工程化改造,使其特异性靶向肿瘤细胞,最常用的是通过单链可变片段(scFv)识别肿瘤相关抗原,该疗法已成功应用于B系血液恶性肿瘤患者,包括白血病、淋巴瘤和多发性骨髓瘤。
然而,复发/难治性(R/R)T细胞恶性肿瘤的治疗效果仍不理想。一个重大挑战是恶性T细胞与正常T细胞之间存在共享抗原,导致CAR-T 细胞之间的自相残杀。
此外,患者白细胞分离产物中存在恶性T细胞可能增加复发风险。输注后,患者可能出现严重的T细胞再生障碍,使本就免疫功能低下的癌症患者更加免疫缺陷。本综述探讨了基于CAR的细胞疗法,包括免疫效应细胞(IEC)如常规T细胞亚群、自然杀伤(NK)细胞、自然杀伤T(NKT)细胞、细胞因子诱导的杀伤(CIK)细胞以及用于T细胞恶性肿瘤的T细胞。
我们讨论了多抗原靶向、新兴技术以及最新的临床试验,以期改善针对T系肿瘤的基于CAR的治疗。
Chimeric antigen receptor (CAR) T-cell therapy utilizes synthetic biology techniques to engineer T cells to specifically target tumor cells using most commonly single-chain variable fragments (scFvs) to recognize tumor-associated antigens, which has been successfully applied to patients with B-lineage hematologic malignancies including leukemia, lymphoma and multiple myeloma.
However, treatment outcomes for relapsed or refractory (R/R) T-cell malignancies remain suboptimal. A significant challenge is the shared antigens between malignant and normal T cells, leading to fratricide among CAR T cells.
Moreover, the presence of malignant T cells in patients' leukapheresis may increase risk of relapse. Post-infusion, patients may experience severe T-cell aplasia, rendering the cancer patients who are generally immunocompromised even more immunodeficient. This review article explores CAR-based cellular therapy, including immune effector cells (IECs) such as conventional T cell subsets, natural killer (NK) cells, natural killer T (NKT) cells, cytokine-induced killer (CIK) cells, and T cells for T-cell malignancies.
We discuss multiple antigen-targeting, emerging technologies, and the latest clinical trials in attempt to improve CAR-based therapy for T-lineage neoplasms.
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