Delving into the Latest Updates on Msctrail(University College, London) with Synapse

Overview

Basic Info

Drug Type

Mesenchymal stem cell therapy

Synonyms-

Target

TRAIL

Action

modulators

Mechanism

TRAIL modulators(Tumor necrosis factor ligand superfamily member 10 modulators), Gene transference(Gene transference)

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication-

Inactive Indication

Adenocarcinoma of Lungmetastatic non-small cell lung cancer

Originator Organization

University College London

Active Organization-

Inactive Organization

University College London

License Organization-

Drug Highest PhasePendingPhase 1/2

First Approval Date-

Regulation-

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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.

Start Date05 Mar 2019

Sponsor / Collaborator

University College London

100 Clinical Results associated with Msctrail(University College, London)

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100 Translational Medicine associated with Msctrail(University College, London)

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100 Patents (Medical) associated with Msctrail(University College, London)

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8

Literatures (Medical) associated with Msctrail(University College, London)

01 Dec 2020·Stem cell research & therapyQ2 · MEDICINE

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

Q2 · MEDICINE

ArticleOA

Author: Patrick, P Stephen ; Edwards, Adam ; Janes, Sam M ; Sanderson, Tom ; Weil, Benjamin D ; Dickson, John C ; Kolluri, Krishna K ; Lythgoe, Mark F ; Lowdell, Mark ; Sage, Elizabeth K ; 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.

01 Dec 2019·Anticancer researchQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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.

01 Jul 2016·CytotherapyQ3 · MEDICINE

Cryopreservation of human mesenchymal stromal cells expressing TRAIL for human anti-cancer therapy

Q3 · MEDICINE

Article

Author: Janes, Sam M ; Lowdell, Mark W ; Kolluri, Krishna K ; Lourenco, Sofia Da Silva ; Yuan, Zhengqiang ; Sage, Elizabeth K

BACKGROUND AIMS:

Mesenchymal stromal cells (MSCs) are being extensively researched for cell therapy and tissue engineering. We have engineered MSCs to express the pro-apoptotic protein tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and are currently preparing this genetically modified cell therapy for a phase 1/2a clinical trial in patients with metastatic lung cancer. To do this, we need to prepare a cryopreserved allogeneic MSCTRAIL cell bank for further expansion before patient delivery. The effects of cryopreservation on a genetically modified cell therapy product have not been clearly determined.

METHODS:

We tested different concentrations of dimethyl sulfoxide (DMSO) added to the human serum albumin ZENALB 4.5 and measured post-thaw cell viability, proliferation ability and differentiation characteristics. In addition, we examined the homing ability, TRAIL expression and cancer cell-killing capacities of cryopreserved genetically modified MSCs compared with fresh, continually cultured cells.

RESULTS:

We demonstrated that the post-thaw viability of MSCs in 5% DMSO (v/v) with 95% ZENALB 4.5 (v/v) is 85.7 ± 0.4%, which is comparable to that in conventional freezing media. We show that cryopreservation does not affect the long-term expression of TRAIL and that cryopreserved TRAIL-expressing MSCs exhibit similar levels of homing and, importantly, retain their potency in triggering cancer cell death.

CONCLUSIONS:

This study shows that cryopreservation is unlikely to affect the therapeutic properties of MSCTRAIL and supports the generation of a cryopreserved master cell bank.

100 Deals associated with Msctrail(University College, London)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of Lung	Phase 2	United Kingdom	University College London	05 Mar 2019
metastatic non-small cell lung cancer	Phase 2	United Kingdom	University College London	05 Mar 2019