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:Novel insights into cancer stem cells targeting: CAR-T therapy and epigenetic drugs as new pillars in cancer treatment.
Novel insights into cancer stem cells targeting: CAR-T therapy and epigenetic drugs as new pillars in cancer treatment.
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癌症干细胞(CSCs)代表存在于肿瘤主体中最具侵袭性的亚群,保留着侵袭能力、转移潜能以及负责治疗耐药的高表达药物外排泵。由于标准治疗方案无法有效清除该亚群,癌症仍是一种无法治愈的疾病。选择性靶向CSCs仍是癌症研究领域尚未满足的需求。异常的表观遗传重编程促进CSCs的起始和维持,使其能够逃避免疫系统防御。能够诱导对这一干细胞样小亚群进行选择性抑制的有前景的治疗方法包括单独免疫治疗或与表观遗传化合物联合使用。这些策略基于仅存在于CSC而不存在于其他癌细胞或正常细胞中的表位和/或表观遗传改变的特定表达。因此,将CAR-T 免疫治疗与表观遗传探针相结合的联合方案可能克服治疗无效的障碍,朝着对具有已知CSC特定改变的患者实施更精准医学的方向迈进。在这篇观点文章中,我们将对表观免疫治疗在富含CSCs的肿瘤中的未来应用及其潜在副作用、局限性和治疗耐药的发展提供新的见解。
Cancer stem cells (CSCs) represent the most aggressive subpopulation present in the tumor bulk retaining invasive capabilities, metastatic potential and high expression levels of drug efflux pumps responsible for therapy resistance. Cancer is still an incurable disease due to the inefficacy of standard regimens that spare this subpopulation. Selective targeting of CSCs is still an unmet need in cancer research field.
Aberrant epigenetic reprogramming promotes the initiation and maintenance of CSCs, which are able to escape the immune system defense. Promising therapeutic approaches able to induce the selective inhibition of this stem-like small subset include immunotherapy alone or in combination with epigenetic compounds. These strategies are based on the specific expression of epitopes and/or epigenetic alterations present only in the CSC and not in the other cancer cells or normal cells.
Thus, the combined approach utilizing CAR-T immunotherapy along with epigenetic probes may overcome the barriers of treatment ineffectiveness towards a more precision medicine approach in patients with known specific alterations of CSCs. In this perspective article we will shed new lights on the future applications of epi-immunotherapy in tumors enriched in CSCs, along with its potential side-effects, limitations and the development of therapy resistance.
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