决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:Molecular-genetic Characterization in Patients Undergoing CAR-T Cell Infusion
Molecular-genetic Characterization in Patients Undergoing CAR-T Cell Infusion
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⚠ 该试验的登记信息已有 21 个月未更新, 页面上显示的「招募中」可能已经失效。联系研究中心之前,建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项分期未标注的注册临床试验,评估细胞治疗用于血液系统恶性肿瘤的安全性、可行性及初步疗效。当前状态:招募中。计划入组 150 例。试验地点:欧洲 · 博洛尼亚(共 1 个中心)。登记号:NCT05807789。
不限性别 · ≥ 18 Years 且 ≤ 70 Years
纳入标准:年龄≥18岁;因血液系统疾病住院,并在博洛尼亚IRCCS AOU先进细胞治疗部门接受已获上市许可的CAR-T 细胞输注治疗;明确同意参加研究并签署知情同意书。排除标准:原登记未列明特定排除标准。
Inclusion Criteria: 1. Patients aged ≥ 18 years. 2. Patients with haematological pathology hospitalized for CAR-T cell infusion therapeutic program (with Marketing Authorization) at the Departmental Program of Advanced Cellular Therapies, of the IRCCS AOU of Bologna 3. Patients with express consent to participate in this study, acquired by signing the informed consent. Exclusion Criteria: \-
以上为辅助阅读译文。是否适合入组须由主治医生判断,最终以登记平台与研究者确认为准。
主要终点:Genomic studies · Genomic studies in peripheral blood samples taken from patients affected by hematological malignancies undergoing CAR-T cell therapy, in order to identify correlations between neoplastic cell signatures and response to therapy (evaluated according to laboratory and instrumental standards). · 3 years;Study of CAR+ and CAR- lymphoid populations and of myeloid populations · Study of CAR+ and CAR- lymphoid populations and of myeloid populations with single-cell RNA sequencing platforms in peripheral blood samples in order to understand the cellular dynamics related to clinical outcomes such as response to therapy (evaluated according to laboratory and instrumental standards) and adverse events (CRS, ICANS, sHLH, coagulopathy, cytopenias, and autoimmune dyscrasias). · 3 years
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近年来,离体细胞培养及细胞工程方法日益先进,推动了CAR-T(CAR-T 细胞)疗法等新型细胞治疗平台的发展。CAR-T 疗法使用经工程化改造、表达针对特定抗原嵌合受体的T淋巴细胞;理论上可用于治疗各类肿瘤,目前更广泛用于血液系统恶性肿瘤。CAR-T 疗法的一项创新是“活药物”概念:细胞既作为药物发挥作用,又帮助建立针对肿瘤的特异性免疫。该疗法可通过不受HLA介导抗原识别限制的机制,补充患者对肿瘤控制不足的免疫能力。然而CAR-T 治疗也可能引起严重甚至致命的不良事件,包括细胞因子释放综合征(CRS)、B细胞缺失(低丙种球蛋白血症)、神经系统不良反应、血液学毒性和感染。考虑到不良事件不可忽视,且超过50%的患者可能失去已获得的疗效,需要通过提高疗效并降低毒性改善CAR-T 治疗。实现这两项目标,需要了解肿瘤细胞耐药机制、CAR-T 细胞生物学,以及其相互作用的细胞(微环境)和非细胞系统。
In recent years, the application of increasingly advanced methods of ex-vivo cell culture and cell engineering has made it possible to develop new cellular therapeutic platforms including the "CAR (Chimeric Antigen Receptor) - T cell therapy". CAR-T cell therapy is a therapy that uses T lymphocytes engineered to express a chimeric receptor directed against a specific antigen, theoretically applicable to the treatment of all neoplasms but currently more widely used in the treatment of haematological malignancies. One of the most innovative aspects introduced with CAR-T cell therapy is that of living-drug, cells that act as a drug as well as a means to build specific immunity against the neoplasm. The advantages of this therapy are therefore represented by the possibility of refueling the patient's immunity, deficient in the control of the neoplastic disease, with lymphocytes capable of expressing an antineoplastic activity with mechanisms not subject to restriction of HLA-mediated antigen recognition. However, the use of CAR-T therapies is not free from potentially serious and sometimes lethal adverse events; in the toxicity profile the following are recognizable as peculiar: * cytokine release syndrome (CRS) * B-cell aplasia (hypogammaglobulinemia) * neurological adverse reactions * haematological toxicity * infections. Therefore, considering that on the one hand adverse events are not negligible and on the other hand that a percentage \> 50% of patients lose the response obtained, it is necessary to improve the therapeutic profile of CAR-T cell therapy by increasing its efficacy and reducing its toxicity . Both of these strategies are linked to the understanding of the resistance mechanisms of neoplastic cells, as well as to the biology of CAR-T cells and of all the cellular (microenvironment) and non-cellular systems with which they interact.
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