MB-CART2019.1(MB-CART2019.1) - 药物靶点：CD19 x CD20_在研适应症：B细胞淋巴瘤，弥漫性大B细胞淋巴瘤，慢性淋巴细胞白血病_专利_临床

概要

基本信息

药物类型

自体CAR-T

别名

Anti-CD20-anti-CD19 CAR T cells、CD20-CD19-targeting CAR T Cells、DALY II USA

+ [1]

靶点

CD19 x CD20

作用机制

CD19抑制剂(B淋巴细胞抗原CD19抑制剂)、CD20抑制剂(B淋巴细胞抗原CD20抑制剂)、T淋巴细胞替代物

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [1]

在研适应症

B细胞淋巴瘤弥漫性大B细胞淋巴瘤慢性淋巴细胞白血病+ [3]

非在研适应症-

原研机构

Miltenyi Biotec, Inc.

在研机构

Miltenyi Biomedicine GmbH初创企业

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评优先药物（PRIME） (欧盟)

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关联

6

项与 MB-CART2019.1 相关的临床试验

NCT06508931 / Not yet recruiting临床2期

A Single-arm, Multi-center, Open-label Phase II Study to Determine the Safety and Efficacy of MB-CART2019.1 in Pediatric Subjects With Relapsed/Refractory (r/r) Mature B-cell Neoplasms Who Have Relapsed After One or More Prior Therapies, Including Subjects With Primary Refractory Disease

This is a single-arm, multi-center, open-label Phase II study to determine the safety and efficacy of MB-CART2019.1 in pediatric and adolescent subjects (aged between 6 months and <18 years, ≥6 kg body weight [BW]) with mature B-cell neoplasms and aggressive lymphomas that relapsed after or are refractory to one or more prior therapies, including subjects with primary refractory disease.

开始日期2025-04-01

申办/合作机构

Miltenyi Biomedicine GmbH初创企业

NCT06508775 / RecruitingN/A

Long-Term Follow-up of Patients Treated With Miltenyi Cell and Gene Therapies

The goal of this Long-Term Follow-Up Trial is to assess long-term safety and efficacy of Miltenyi CAR T treatment.

开始日期2024-05-05

申办/合作机构

Miltenyi Biomedicine GmbH初创企业

NCT04844866 / Active, not recruiting临床2期

A Pivotal Phase II Randomised, Multi-centre, Open-label Study to Evaluate the Efficacy and Safety of MB-CART2019.1 Compared to SoC Therapy in Participants With r/r DLBCL, Who Are Not Eligible for HDC and ASCT

This is a pivotal Phase II randomised, multi-centre, open-label study to evaluate the efficacy and safety of MB-CART2019.1 compared to standard of care therapy in participants with relapsed/refractory diffuse large B-cell lymphoma, who are not eligible for high-dose chemotherapy and autologous stem cell transplantation.

开始日期2021-08-18

申办/合作机构

Miltenyi Biomedicine GmbH初创企业

[+1]

100 项与 MB-CART2019.1 相关的临床结果

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100 项与 MB-CART2019.1 相关的转化医学

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100 项与 MB-CART2019.1 相关的专利（医药）

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11

项与 MB-CART2019.1 相关的文献（医药）

2024-11-01·The Lancet Rheumatology

CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series

Article

作者: Auth, Janina ; Fuchs, Florian ; Bergmann, Christina ; Krickau, Tobias ; Hagen, Melanie ; Harrer, Thomas ; Kretschmann, Sascha ; Mackensen, Andreas ; Uder, Michael ; Aigner, Michael ; Bozec, Aline ; Rothe, Tobias ; Horch, Raymund E ; Tur, Carlo ; Tascilar, Koray ; Liphardt, Anna-Maria ; Grieshaber-Bouyer, Ricardo ; Spörl, Silvia ; Müller, Fabian ; Schett, Georg ; Völkl, Simon ; Kuwert, Torsten ; Györfi, Andrea-Hermina ; Chenguiti Fakhouri, Sara ; Taubmann, Jule ; Bäuerle, Tobias ; Coppers, Birte ; Wirsching, Andreas ; Distler, Jörg H W ; Raimondo, Maria G ; Bayerl, Nadine ; Eckstein, Markus ; Berking, Carola ; Atzinger, Armin ; Dees, Clara ; Kharboutli, Soraya

BACKGROUNDCD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis. We present a detailed analysis of the effects of CD19-targeting CAR T-cell therapy in patients with systemic sclerosis.METHODSSix patients with severe diffuse systemic sclerosis with an insufficient response to at least two treatments were consecutively recruited at the Department of Internal Medicine 3, University Hospital Erlangen (Erlangen, Germany) to receive CD19-targeting CAR T-cell treatment (1 × 10⁶ CAR T cells per kg bodyweight). Events were predefined by progression of interstitial lung disease, onset of congestive heart failure, onset of renal failure, onset of arterial hypertension, or initiation of new immunosuppressive or antifibrotic therapy. Event-free time or treatment intensification after study entry was the primary outcome. Key secondary outcomes included changes in the modified Rodnan Skin Score (mRSS), imaging (a component of the assessment of lung fibrosis), laboratory assessments, patient-reported outcomes, and a modified version of the American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline, 3 months, 6 months, 9 months, and 12 months.FINDINGSBetween April 20, 2022, and Nov 8, 2023, six patients with severe diffuse systemic sclerosis (median age 42 years [IQR 36-53]; four men and two women; all White European) were recruited and received CD19-targeted CAR T-cell therapy. The median follow-up time was 487 days (IQR 342-585). No events occurred within the observational period. Probability of improvement in the ACR-CRISS score increased to a median of 100% (IQR 100-100) at 6 months. Median mRSS decreased by 31% (IQR 29-38), corresponding to a median of 8 points (IQR 7-13) within 100 days. The extent of disease on CT scan decreased by a median of 4% (IQR 3-4) due to reduction of ground-glass opacities while the reticular pattern remained stable. Forced vital capacity improved by a median of 195 mL (IQR 18-275) at the latest observational timepoint.INTERPRETATIONWe provide the first evidence that CD19-targeting CAR T-cell therapy might intercept with the progression of fibrotic organ manifestations in patients with systemic sclerosis.FUNDINGDeutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN-Foundation Erlangen, IZKF Erlangen, and Bundesministerium für Bildung und Forschung.

2023-06-27·JAMA

CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome.

Article

作者: Faul, Christoph ; Lengerke, Claudia ; Bornemann, Antje ; Braun, Christiane ; Schmidt, Marina ; Horger, Marius ; Schneider, Janine ; Bethge, Wolfgang ; Stanger, Anna ; Pecher, Ann-Christin ; Atar, Daniel ; Seitz, Christian ; Hensen, Luca ; Klein, Reinhild ; Henes, Joerg ; Lutz, Katrin ; Schairer, Rebekka

ImportanceAutoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting-chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome.ObjectiveTo test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement.Design, Setting, and ParticipantsThis case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity.ExposurePrior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion.Main Outcomes and MeasuresThe patient's response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes.ResultsRapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient's scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%).Conclusions and RelevanceCD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.

2023-01-01·Therapeutic Advances in Neurological Disorders

Repurposing MS immunotherapies for CIDP and other autoimmune neuropathies: unfulfilled promise or efficient strategy?

Review

作者: Lehmann, Helmar C. ; Dalakas, Marinos C. ; Kohle, Felix

Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number of studies that explored the efficacy of DMTs in animal models of AN but also in some CIDP patients. We here review the available preclinical and clinical data of approved MS therapeutics in terms of their applicability to AN, especially CIDP. Promising therapeutic approaches appear to be B cell–directed and complement-targeting strategies, such as anti-CD20/anti-CD19 agents, Bruton’s tyrosine kinase inhibitors and anti-C5 agents, as they exert their effects in the periphery. This is a major advantage because, in contrast to MS, their action in the periphery is sufficient to exert significant immunomodulation.

100 项与 MB-CART2019.1 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
弥漫性大B细胞淋巴瘤	临床2期	荷兰	Miltenyi Biomedicine GmbH初创企业	2021-08-18
弥漫性大B细胞淋巴瘤	临床2期	西班牙	Miltenyi Biomedicine GmbH初创企业	2021-08-18
弥漫性大B细胞淋巴瘤	临床2期	瑞典	Miltenyi Biomedicine GmbH初创企业	2021-08-18
弥漫性大B细胞淋巴瘤	临床2期	立陶宛	Miltenyi Biomedicine GmbH初创企业	2021-08-18
弥漫性大B细胞淋巴瘤	临床2期	匈牙利	Miltenyi Biomedicine GmbH初创企业	2021-08-18
弥漫性大B细胞淋巴瘤	临床2期	法国	Miltenyi Biomedicine GmbH初创企业	2021-08-18
弥漫性大B细胞淋巴瘤	临床2期	波兰	Miltenyi Biomedicine GmbH初创企业	2021-08-18
弥漫性大B细胞淋巴瘤	临床2期	意大利	Miltenyi Biomedicine GmbH初创企业	2021-08-18
慢性淋巴细胞白血病	临床2期	德国	Miltenyi Biomedicine GmbH初创企业	2019-02-25
小淋巴细胞淋巴瘤	临床2期	德国	Miltenyi Biomedicine GmbH初创企业	2019-02-25

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03870945 (EHA2022)	临床1期	复发性B细胞淋巴瘤	12	MB-CART2019.1	(簾襯醖遞顧範廠窪鹽鹹) = 選觸膚鑰願選襯顧廠膚蓋顧憲網衊壓糧醖鏇艱 (淵製顧願襯廠簾淵鏇選 )	-	2022-05-12
NCT03870945 (ASH2020) 人工标引	临床1期	B细胞淋巴瘤 CD19 Positive \| CD20 Positive	12	MB-CART2019.1	(憲淵顧獵餘齋窪築顧構) = CRS grade 1 occurred in 3/6 patients on DL1 and DL2 each, and CRS grade 2 in 2 patients on DL2. 觸窪餘鹹製壓醖範構顧 (糧鏇網憲淵顧艱製鹹餘 ) 更多	积极	2020-11-05
NCT03870945 (ASH2020) 人工标引	临床1期	B细胞淋巴瘤 CD19 Positive \| CD20 Positive	12	MB-CART2019.1		积极	2020-11-05