The purpose of this study is to evaluate the safety and efficacy of CAR T cell treatment targeting CD7 in patients with relapsed or refractory CD7 positive T-cell hematological maliganacies

开始日期2022-05-04

申办/合作机构

上海市第一人民医院

NCT04599556 / Recruiting临床1期IIT

Clinical Trial for the Safety and Efficacy of Anti-CD7 Chimeric Antigen Receptor Cell Therapy for Patients With Relapsed or Refractory CD7 Positive Hematological Malignancy

This is a prospective, open-label, single-center clinical trial. This study will evaluate the safety and efficacy of anti-CD7 CAR-T cells in the treatment of relapsed or refractory CD7 positive T-ALL/LBL, T-NHL and AML. The primary endpoints are dose limiting toxicity (DLT) and the incidence of treatment emergent adverse event (TEAE).

开始日期2021-04-01

申办/合作机构

浙江大学

[+1]

NCT04572308 / Completed临床1期

Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells

This is an open, single-arm, clinical study to evaluate efficacy and safety of anti CD7 CAR-T cell in the treatment of relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (TLBL).

开始日期2020-10-01

申办/合作机构

河北森朗生物科技有限公司

100 项与 CD7阳性T细胞白血病相关的临床结果

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100 项与 CD7阳性T细胞白血病相关的转化医学

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0 项与 CD7阳性T细胞白血病相关的专利（医药）

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项与 CD7阳性T细胞白血病相关的文献（医药）

2022-07-01·Clinical Cancer Research1区 · 医学

Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma

1区 · 医学

Article

作者: Zhang, Mingzhi ; Chen, YuSheng ; Wu, Xiaolong ; Xu, Hanying ; Chen, Dan ; Wang, Xinhua ; Li, Jiwei ; Yang, Lin ; Xiang, Shufen ; Wang, Yinyan ; Yu, Hui ; Meng, Huimin ; Zhang, Lei ; Nan, Feifei ; Li, Ling ; Fu, Xiaorui ; Yan, Jiaqin ; You, Fengtao ; Li, Zhaoming ; Zhang, Bozhen ; Wang, Yu ; Sun, Zhenchang ; Wang, Min ; Zhou, Zhiyuan ; Pan, Guifang ; Chang, Yu ; Li, Xin

AbstractPurpose:Since CD7 may represent a potent target for T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) immunotherapy, this study aimed to investigate safety and efficacy of autologous CD7–chimeric antigen receptor (CAR) T cells in patients with relapsed and refractory (R/R) T-ALL/LBL, as well as its manufacturing feasibility.Patients and Methods:Preclinical phase was conducted in NPG mice injected with Luc+ GFP+CCRF-CEM cells. Open-label phase I clinical trial (NCT04004637) enrolled patients with R/R CD7-positive T-ALL/LBL who received autologous CD7-CAR T-cell infusion. Primary endpoint was safety; secondary endpoints included efficacy and pharmacokinetic and pharmacodynamic parameters.Results:CD7 blockade strategy was developed using tandem CD7 nanobody VHH6 coupled with an endoplasmic reticulum/Golgi-retention motif peptide to intracellularly fasten CD7 molecules. In preclinical phase CD7 blockade CAR T cells prevented fratricide and exerted potent cytolytic activity, significantly relieving leukemia progression and prolonged the median survival of mice. In clinical phase, the complete remission (CR) rate was 87.5% (7/8) 3 months after CAR T-cell infusion; 1 patient with leukemia achieved minimal residual disease–negative CR and 1 patient with lymphoma achieved CR for more than 12 months. Majority of patients (87.5%) only had grade 1 or 2 cytokine release syndrome with no T-cell hypoplasia or any neurologic toxicities observed. The median maximum concentration of CAR T cells was 857.2 cells/μL at approximately 12 days and remained detectable up to 270 days.Conclusions:Autologous nanobody-derived fratricide-resistant CD7-CAR T cells demonstrated a promising and durable antitumor response in R/R T-ALL/LBL with tolerable toxicity, warranting further studies in highly aggressive CD7-positive malignancies.

2020-08-01·Zhongguo shi yan xue ye xue za zhi

[Killing Effect of A CD7 Chimeric Antigen Receptor-Modified NK-92MI Cell Line on CD7-Positive Hematological Malignant Cells].

Article

作者: Yang, Lin ; Wang, Xing-Bing ; Liu, Na-Na ; Pan, Gui-Fang ; Wang, Min ; You, Feng-Tao ; Liu, Xin ; Zhu, Xin-Ying ; Wang, An-You

题目靶向CD7的嵌合抗原受体NK-92MI细胞对CD7阳性血液系统恶性肿瘤细胞的杀伤作用.目的探讨特异性靶向CD7分子的嵌合抗原受体（CD7-CAR）修饰的NK-92MI细胞对CD7阳性血液系统恶性肿瘤细胞的杀伤作用.方法分别收集5例CD7⁺的急性T淋巴细胞白血病（acute T-lymphoblastic leukemia，T-ALL）、10例急性髓细胞白血病（acute myeloid leukemia，AML）和6例T细胞淋巴瘤三类血液系统恶性肿瘤细胞，经实验室离心处理、培养后检测肿瘤细胞表面靶标的表达水平；应用7-AAD、CD56-APC、CD3-FITC、IgG Fc-PE流式细胞术检测NK-92MI和CD7-CAR-NK-92MI细胞的转染效率；使用PE Annexin V Apoptosis Detection Kit检测CD7-CAR-NK-92MI细胞对CD7阳性血液肿瘤细胞的体外杀伤效率。用CBA试剂盒检测杀伤后NK-92MI和CD7-CAR-NK-92MI细胞因子白介素-2（IL-2）、干扰素（IFN-γ）及颗粒酶B的分泌差异.结果CD7-CAR修饰的NK-92MI细胞对CD7⁺ T-ALL、AML、T细胞淋巴瘤肿瘤细胞的杀伤效率明显高于未被修饰的阴性对照组NK-92MI细胞，其差异具有统计学意义（P＜0.05）；与未被修饰的NK-92MI细胞相比，经CD7-CAR修饰的NK-92MI细胞分泌的细胞因子中，IFN-γ和颗粒酶B的水平明显升高（P＜0.05）.结论经CD7-CAR修饰的NK-92MI细胞对CD7⁺ T-ALL、AML和T淋巴瘤细胞的杀伤效率显著提高，且具有特异性靶向作用.

2019-12-01·Best Practice & Research Clinical Haematology4区 · 医学

Chimeric antigen receptor T cells (CAR-T) for the treatment of T-cell malignancies

4区 · 医学

Review

作者: Cooper, Mathew L ; DiPersio, John F

At present, the only curative therapy for patients with T-cell malignancies is allogeneic stem cell transplant, which has associated risks and toxicities. Novel agents have been tried in relapsed T-cell acute lymphoblastic leukemia (T-ALL), but only one, with 20%-30% complete remission rates, has been approved by the US Food and Drug Administration. T-ALL is a heterogeneous disease, but it has universal overexpression of CD7 as well as several other T-cell markers, such as CD2 and CD5. T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown great potential for inducing both remissions and even long-term relapse-free survival in patients with B-cell leukemia and lymphoma. UCART7 for CD7⁺ T-cell malignancies is in development for treatment of relapsed T-ALL in children and adults. It may also have potential in other CD7⁺ hematologic malignancies that lack both effective therapies and targeted therapies. The challenges encountered and progress made in developing a novel fratricide-resistant "off-the-shelf" CAR-T (or UCART7) that targets CD7⁺ T-cell malignancies are discussed here.

项与 CD7阳性T细胞白血病相关的新闻（医药）

2023-04-12

·SYNAPSE

CAR-T治疗领域再获进展，雅科生物发表其CD7 CAR-T细胞2年随访结果

4月11日，雅科生物科技公司宣布了采用该公司CD7 CAR-T细胞治疗技术医治的T细胞白血病患者的2年随访结果，这一临床结果发表在知名学术期刊《Journal of Hematology & Oncology》（Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia1），报告了该疗法在2年随访后的长期安全性和疗效。成人T细胞白血病（adult T-cell leukemia，ATL）是一种与人T细胞白血病病毒Ⅰ（HTLV-Ⅰ）感染直接相关、发生于成人的特殊类型淋巴系统恶性克隆增殖性疾病，其病变主要发生在外周血淋巴细胞，亦可侵及骨髓。该病多依据临床分型不同而决定治疗策略，慢性型或冒烟型患者多采用对症支持治疗，以积极控制感染和改善脏器功能为主，当出现病情进展或急性转变时，方可考虑采用积极治疗措施。急性型或淋巴瘤型ATL虽采用化学、生物学等积极治疗措施，但疗效不佳，中位生存期2～6个月。 CAR-T疗法，即嵌合抗原受体T细胞免疫疗法，英文全称Chimeric Antigen Receptor T-Cell Immunotherapy。这是一种治疗肿瘤的新型精准靶向疗法，近几年通过优化改良在临床肿瘤治疗上取得很好的效果。CAR-T疗法是一种非常有前景的、可能治愈癌症的新型肿瘤免疫治疗方法。 CD7 CAR T细胞治疗技术通过基因修饰T细胞使其能够识别和攻击表达CD7的癌细胞，在治疗CD7阳性的T细胞恶性肿瘤和急性髓系白血病（AML）上具有很大的潜力。在先前的一项I期试验报告中，供体来源的CD7定向嵌合抗原受体（CAR）T细胞在难治或复发的T细胞急性淋巴细胞白血病（r/r T-ALL）患者中显示出可行性和早期疗效。在这项研究中，20名参与者接受了CD7 CAR-T细胞输注。经过中位随访时间为27.0个月后，总体反应率和完全缓解率分别为95％（19/20名患者）和85％（17/20名患者），其中35％（7/20）的患者进行了干细胞移植。6名患者出现疾病复发，复发中位时间为6（范围为4.0-10.9）个月，其中4名患者发现肿瘤细胞上的CD7表达丢失。治疗后24个月的无进展生存率（PFS）和总生存率（OS）分别为36.8％（95％CI，13.8-59.8％）和42.3％（95％CI，18.8-65.8％），中位PFS和OS分别为11.0（95％ CI，6.7-12.5）个月和18.3（95％CI，12.5-20.8）个月。 CAR-T疗法无疑为癌症治疗带来新希望，然而，这种疗法也有严重不良反应，主要是细胞因子释放综合征（也叫细胞因子释放风暴，CRS）和神经毒性。在本实验中，治疗后30天内报告的不良事件包括3-4级CRS（10％）和1-2级移植物抗宿主病（GVHD，60％）。雅科生物表示，此项长期临床研究充分证明该公司的CD7 CAR T细胞回输后具有在体内扩增好、能持续存活的优势。同时，此项临床研究也揭示，伴随此项CAR T细胞治疗的感染问题需要在临床管理中得到充分重视和及时处理。参考资料： https://mp.weixin.qq.com/s/Vfy84pLumsrPG3f7YlF4Dw