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:Glioblastoma, an opportunity T cell trafficking could bring for the treatment.
Glioblastoma, an opportunity T cell trafficking could bring for the treatment.
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本综述总结了 CAR-T 细胞治疗 GBM 的最新进展,并讨论了为何该策略有望成为此类脑肿瘤下一代免疫治疗的支柱。
胶质母细胞瘤(GBM)浸润脑部重要结构、位于难以触及的解剖区域且分子异质性显著,无疑是最致命的癌症之一。GBM利用血脑屏障(BBB)限制化疗药物到达肿瘤部位,并形成独特微环境,为癌细胞生存提供条件、使肿瘤细胞逃避免疫监视。
经协商一致,纳入99篇符合资格标准的文献,并根据研究设计和证据水平进行分类。
鉴于这些特征,免疫疗法一度因有望治疗GBM而受到前所未有的关注,但这种热情很快减弱。研究发现,癌细胞可通过淋巴管招募免疫抑制性淋巴细胞进入脑内,巧妙操纵治疗药物引发的抗肿瘤应答,使GBM成为研究免疫治疗耐药的良好模型。然而,发现淋巴管也带来一种设想:将效应T淋巴细胞过继招募至肿瘤微环境。由此,工程和克隆技术得以应用,设计用于GBM治疗的特异性人工T细胞疗法——嵌合抗原受体(CAR)T细胞。
本文综述GBM CAR-T 细胞治疗的近期进展,并讨论为何这一策略有望成为该类脑肿瘤下一代免疫疗法的支柱之一。
Infiltrating into the vital structure of the brain, located in the inaccessible anatomical region, and having molecular heterogeneity, glioblastoma (GBM) -with no doubt- is one of the deadliest cancers. Using the blood and brain barrier (BBB), GBM makes a shield to restrict the reach of chemotherapeutic agents to the tumor site and evolves a unique microenvironment to furnish all the essentials for cancer cells survival to conceal neoplastic cells from immunosurveillance.
99 papers which met the criteria of eligibility were included in this review by consensus. The included articles were classified based on their design and level of evidence.
Given this characteristic, immunotherapies for a while enjoyed unprecedented attention as a solution for GBM treatment; however, it did not take long before the enthusiasm for their application was muted. It became apparent that cancer cells intelligently find a way to manipulate the anti-tumor responses of agents by attracting immunosuppressive lymphocytes into the brain using the lymphatic vessels. This event makes GBM a good model for immunotherapy resistance. However, the presence of lymphatic vessels has fired up an idea of the adoptive attraction of effector T lymphocytes to the tumor milieu. This was when engineering and cloning technologies, which have given life to one of the recent treatment strategies using artificial T cells named chimeric antigen receptors (CAR) T-cells, came to action to design specific CAR T-cells for the treatment of GBM.
The present review summarizes the recent advances in CAR T-cell-based treatments in GBM and discusses why this approach could be positioned as a pillar of the next-generation of immunotherapies for this type of brain tumor.
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