Msctrail(University College, London)(Msctrail(University College, London))

概要

基本信息

药物类型

间充质干细胞疗法

别名-

靶点

TRAIL

作用方式

调节剂

作用机制

TRAIL调节剂(肿瘤坏死因子配体超家族成员10调节剂)、Gene transference(基因转移)

治疗领域

肿瘤呼吸系统疾病

在研适应症-

非在研适应症

肺腺癌转移性非小细胞肺癌

原研机构

University College London

在研机构-

非在研机构

University College London

权益机构-

最高研发阶段无进展临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

1

项与 Msctrail(University College, London) 相关的临床试验

NCT03298763

/ Unknown status临床1/2期IIT

Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer

The aim of the study is to evaluate the safety and anti-tumour activity of MSCTRAIL in addition to chemotherapy in metastatic Non-small cell lung cancer (NSCLC) patients in a Phase I/II clinical trial.
In the phase I study, patients will receive cisplatin and pemetrexed on day one followed by MSCTRAIL cells on day 2. This constitutes one cycle of treatment. Each patient will receive 3 cycles of treatment at 21 day intervals. The aim of phase 1 is to estimate the recommended Phase II dose (RP2D) of MSCTRAIL in combination with pemetrexed/cisplatin chemotherapy.
During the phase II study patients will be randomised to either the intervention or the control arm of the study. All patients in both arms will receive cisplatin and pemetrexed on day one of treatment. Patients randomised to the intervention arm will receive the recommended dose of MSCTRAIL from Phase I on day 2 whilst those in the control arm will receive a placebo. As this is a double blind trial both patients and the clinical team will not know whether they are receiving MSCTRAIL or a placebo product. The aim of phase 2 is to assess tolerability and preliminary efficacy of MSCTRAIL in combination with pemetrexed/cisplatin chemotherapy.

开始日期2019-03-05

申办/合作机构

University College London

100 项与 Msctrail(University College, London) 相关的临床结果

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100 项与 Msctrail(University College, London) 相关的转化医学

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100 项与 Msctrail(University College, London) 相关的专利（医药）

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10

项与 Msctrail(University College, London) 相关的文献（医药）

2026-06-01·CYTOTHERAPY

A first-in-human phase I clinical trial investigating the safety and efficacy of repeat dosing MSCTRAIL cell therapy in addition to chemotherapy and immunotherapy in patients with advanced lung cancer

Article

作者: Riddell, Anne ; Selway-Clarke, Hugh ; Jacob, Joseph ; Kolluri, Krishna ; Janes, Sam M ; Kalber, Tammy ; Benafif, Sarah ; Graham, Rebecca N ; Weil, Ben ; Gear, David ; Lowdell, Mark W ; Jones, Joanne L ; Yamada, Daisuke ; Szmul, Adam ; Wheeler, Graham ; Mullin, Monica L ; Chowdary, Pratima ; Popova, Bilyana ; Galani, Sevasti ; Nair, Arjun ; Khaw, Chuen Ryan ; Howlett, Sarah K ; Sage, Beth ; Davies, Alice ; Day, Alexander G ; Forster, Martin D ; Krebs, Matthew G

BACKGROUND AND AIMS:

Despite recent progress, advanced non-small cell lung cancer (NSCLC) has poor survival outcomes, necessitating the development of novel therapies. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces cancer cell death and can be delivered to tumors by mesenchymal stromal cells (MSCs) due to the cells' migratory properties. This first-in-human phase I trial assessed safety and dose of umbilical cord-derived MSCs expressing TRAIL (UC-MSCTRAIL) alongside standard NSCLC therapy.

METHODS:

Participants performance status 0-1 with treatment-naïve, inoperable stage IIIB/IV NSCLC received UC-MSCTRAIL infusions with each cycle of chemotherapy and immunotherapy, up to 3 cycles. A dose de-escalation design was used. Exploratory in vitro and in vivo studies further characterized UC-MSCTRAIL properties.

RESULTS:

Six participants enrolled; four received 4 × 10⁸ cells/infusion (median 5.4 × 10⁶ cells/kg), and two received 2 × 10⁸ cells/infusion (median 2.4 × 10⁶ cells/kg). Early termination occurred due to asymptomatic pulmonary emboli (N = 5), which included two patients that were anticoagulated as a protocol amendment with prophylactic low molecular weight heparin (enoxaparin 40 mg) and rivaroxaban 20 mg, respectively. Exploratory analyses found no clear pro-coagulant or immunogenic mechanisms, though participants receiving UC-MSCTRAIL had elevated inflammatory markers.

CONCLUSION:

This first-in-human study of UC-MSCTRAIL in advanced lung cancer was terminated early due to high prevelance of pulmonary embolism. THough exact mechanism remains unclear, UC-MSCTRAIL may have contributed to a pro-inflammatory environment in participants already at elevated risk of thrombosis due to malignancy. Future MSC-based therapies should incorporate close monitoring for asymptomatic thrombosis and follow a dose escalation design for safety. Safety concerns underscore the need for further research.

2020-12-01·Stem cell research & therapy2区 · 医学

Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT

2区 · 医学

ArticleOA

作者: Patrick, P Stephen ; Janes, Sam M ; Edwards, Adam ; Sanderson, Tom ; Weil, Benjamin D ; Dickson, John C ; Kolluri, Krishna K ; Lowdell, Mark ; Sage, Elizabeth K ; Lythgoe, Mark F ; Kalber, Tammy L ; Zaw Thin, May

Abstract:

Background:

MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate89Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma.

Methods:

MSCTRAIL were radiolabelled with89Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of89Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo.

Results:

MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of89Zr-oxine labelling on cell proliferation rate was amount- and time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections.

Conclusions:

89Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability.

2019-12-01·Anticancer research4区 · 医学

Evaluation of Combination Treatment Effect With TRAIL-secreting Mesenchymal Stem Cells and Compound C Against Glioblastoma

4区 · 医学

Article

作者: Ryu, Chung Heon ; Ahn, Stephen ; Han, Hye Rim ; Jeun, Sin-Soo ; Park, Soon A

BACKGROUND/AIM:

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis of cancer cells and, when used in combination with other anticancer drugs, is regarded as an effective strategy for anticancer treatment. In this study, we investigated the efficacy of combination treatment with TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL) and compound C, an AMP-activated protein kinase (AMPK inhibitor), on glioblastoma.

MATERIALS AND METHODS:

The anticancer effect using MSC-TRAIL and compound C on glioma was evaluated in vitro and on in vivo models.

RESULTS:

Combination treatment of MSC-TRAIL and compound C increased apoptosis by enhancing expression of B-cell lymphoma 2 (BCL2)-associated X protein (BAX) and reducing that of anti-apoptotic proteins cellular FLICE-inhibitory protein (FLIP), X-linked inhibitor of apoptosis (XIAP), and BCL2 in glioma. In addition, MSC-TRAIL and compound C combination increased caspase-3 cleavage and apoptotic cells in a mouse glioma model compared with the group treated with the agents alone.

CONCLUSION:

Our results suggest that MSC-TRAIL and compound C are a novel combination for treatment of glioma.

100 项与 Msctrail(University College, London) 相关的药物交易

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