Ben Weil

Royal Free London NHS Foundation Trust | Royal Free · Centre for Cell, Gene and Tissue Therapeutics

Cell therapy is a promising tool to prevent and treat heart failure in congenital heart disease. We report the first case of intramyocardial injection of allogeneic mesenchymal stromal cells as rescue therapy in a neonate with ischemic heart failure following arterial switch procedure for isolated transposition of the great arteries. (Level of Diff...

Background: With therapeutic hypothermia (HT) for neonatal encephalopathy, disability rates are reduced, but not all babies benefit. Pre-clinical rodent studies suggest mesenchymal stromal cells (MSCs) augment HT protection. Aims: The authors studied the efficacy of intravenous (IV) or intranasal (IN) human umbilical cord-derived MSCs (huMSCs) a...

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 pr...

Objectives: Fibrosis of the vocal fold lamina propria reduces vocal cord vibration resulting in a chronically hoarse voice. We describe a novel approach using umbilical cord-derived mesenchymal stem cells in a dehydrated collagen matrix (cellogen) to reconstruct the delicate balance of extracellular matrix within the vocal fold lamina propria whil...

Unlike conventional pharmaceuticals, biologics and Advanced Therapy Medicinal Products (ATMPs) are required to meet a standard of “potency” as part of the final release criteria at completion of manufacture. During early phase clinical trials, most regulatory agencies have been willing to accept very immature potency assays with an expectation that...

Background aims: Cell therapies have the potential to improve reconstructive procedures for congenital craniofacial cartilage anomalies such as microtia. Adipose-derived stem cells (ADSCs) and auricular cartilage stem/progenitor cells (CSPCs) are promising candidates for cartilage reconstruction, but their successful use in the clinic will require...

Cell and gene therapy (CGT) continues to be an expanding field of biotech, however, current therapies are frequently associated with complex manufacture and distribution platforms which result in high costs of goods. To provide the benefits from economies of scale, quality control batch testing, and an ‘off-the-shelf’ supply model, allogeneic treat...

Cell and gene therapy (CGT), within the biopharmaceutical industry, continues to gain traction with the success of chimeric antigen receptor (CAR) T-cell therapies from Novartis and Gilead, stem/stromal cells from Takeda (formerly TiGenix), limbal stem cells from Chiesi, oncolytic virus from Amgen, and many more. However, these novel therapies were...

Background & Aim Lack of comprehensive product knowledge in clinical applications may result in toxicity or reduced drug efficacy. The distributive fate and retention of cell/gene therapies is rarely evaluated, with very few studies assessing their biodistribution in a clinical setting. Understanding the location and retention of cells can result i...

Purpose MSCTRAIL is a new stem cell-based therapy for lung cancer, currently in phase I evaluation (ClinicalTrials.gov ref: NCT03298763). Biodistribution of cell therapies is rarely assessed in clinical trials, despite cell delivery to the target site often being critical to presumed mechanism of action. This preclinical study demonstrates that MSC...

There is growing interest in the regenerative potential of adipose-derived stem cells (ADSCs) for wound healing applications. ADSCs have been shown to promote revascularization, activate local stem cell niches, reduce oxidative stress, and modulate immune responses. Combined with the fact that they can be harvested in large numbers with minimal don...

TPS9116 Background: Mesenchymal stromal cells (MSCs) migrate to and incorporate into tumour stroma allowing them to act as vehicles for delivering anti-cancer therapies. TNF-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in malignant cells however short biological half-life has its limited therapeutic efficacy. We have tran...

Translation of cell and gene therapies from pre-clinical experiments to clinical trials and final drug licensing brings requires the development, verification and even validation of the assays essential for the definition of the drug product. The technical and scientific challenges in doing this are far greater than they seem at first and are compo...

Introduction Lung cancer is the leading cause of cancer death worldwide with over 70% presenting with incurable disease and few effective treatments. We previously demonstrated that mesenchymal stem cells (MSCs) transduced to express TNF-related apoptosis inducing ligand (TRAIL), will home to and induce apoptosis of tumour cells in vitro and reduce...

Cell therapy has the potential to treat a wide variety of unmet therapeutic indications that affect a growing number of people globally. Many of these therapies require purification steps to separate specific cell types from heterogeneous populations. This thesis investigates current affinity purification platforms to isolate human pluripotent stem...

Aim: To present an integrated techno-economic analysis assessing the feasibility of affinity purification technologies using the manufacture of induced pluripotent stem cell-derived progenitor photoreceptors for retinal dystrophies as a case study. Materials & methods: Sort purity, progenitor yield and viable cell recovery were investigated for...

The cell therapy industry would greatly benefit from a simple point of care solution to remove dimethylsulphoxide (DMSO) from small-volume thawed cell suspensions before injection. A novel dead-end filtration device has been designed and validated, which takes advantage of the higher density of thawed cell suspensions to remove the DMSO and protein...

An ever increasing number of cellular therapies are in development for the treatment of a wide variety of diseases. One of the major challenges facing the translation of whole cell products into licensed therapies is the development of efficient, scalable purification processes. Current devices struggle to provide high resolution separations whilst...

A major challenge facing the development of effective cell therapies is the efficient differentiation of pluripotent stem cells (PSCs) into pure populations. Lowering oxygen tension to physiological levels can affect both the expansion and differentiation stages. However, to date, there are no studies investigating the knock-on effect of culturing...