Expansion of the GMP facility for Stem Cell Therapy at Imperial College

Lead Research Organisation: Imperial College London

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

Imperial College was awarded £1077K towards expansion of the GMP facility for stem cell therapy at the Hammersmith Campus. This will help to alleviate the current crisis in capacity, and the proposed investment would bring substantial added value.|Stem cell research and its translational embodiment (regenerative medicine) are presently among the most auspicious aspects of discovery biology and its application to the bedside.|Cell-based therapies have long-standing and venerable importance in the treatment of hematological disorders, including the restitution of bone marrow after cancer chemotherapy. Bone marrow-derived stem cells include not only hematopoietic stem cells (HSCs) that reconstitute the blood-forming lineages but also bone marrow stromal cells (mesenchymal stem cells; MSCs). Both have been deployed as potential therapies across a wide spectrum of human disorders, in successful Phase I and Phase II clinical trials.|The scientific principles underpinning these cells beneficial effects are a matter of intensive study, but include the secretion of angiogenic, cytoprotective, immunosuppressive, and|wound-healing factors, beyond merely the suggested possibility, in some cases, of bona fide regeneration. By contrast, the ability to create new heart muscle or neurons, for example, is unquestioned in the case of embryonic stem (ES) cells derived from the|blastocyst or in the case of novel progenitor and stem cells that have been newly defined in the heart, brain, and other organs. Furthermore, the forced expression of stemness |transcription factors in adult fibroblasts or other adult somatic cells and the resulting creation of induced pluripotent stem cells provides uncanny opportunities to investigate patient-specific ES cell-like cells, as new models of human disorders or as new avenues of|therapy.|In short, the inherent attractiveness, logic, allure and scientific timeliness of cell-based approaches offers the promise of revolutionary advances in regenerative medicine, for|many of the most complex, prevalent, and challenging diseases.

Publications

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Apperley JF (2011) Regulation of donor participation in research studies: is there another way? in Bone marrow transplantation

 
Description European committe for the release criteria of mesenchymal stem cells for clinical use
Geographic Reach Europe 
Policy Influence Type Membership of a guidance committee
 
Description European consensus group on optimal mobilisation schedules
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Clinical trial of DNA vaccine for WT1 in haematological malignancies
Amount £460,000 (GBP)
Organisation Leukaemia and Lymphoma Research 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2011 
End 04/2013
 
Description Programme grant
Amount £750,000 (GBP)
Organisation Leukaemia and Lymphoma Research 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2010 
End 04/2013
 
Description Project grant
Amount £250,000 (GBP)
Organisation The Kay Kendall Leukaemia Fund 
Sector Academic/University
Country United Kingdom
Start 08/2010 
End 07/2013
 
Title CMV specific T-cells 
Description T-lymphocytes directed against antigens presented by CMV infected cells 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact Optimistion of cell selection and explansion has facilitated development of a novel phase I/II clinical trial to investigate the use of autologous anti-CMV specific T-cells for CMV disease after allogeneic stem cell transplant 
 
Title NK cells 
Description NK cells are a sub-population of lymphocytes thought to have anti-tumour activity 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Scale-up of NK cell production has now completed enabling the development of a phase I/II clinical study. 
 
Title Selective allo-depleted stem cell product for stem cell transplant 
Description This establishes a clinical-scale process capable of highly efficient, reproducible, selective removal of alloreactive lymphocytes from lymphocyte transplant products performed under current Good Manufacturing Practice 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact We are participating in a multi-centre study of the use of these cells in clinical transplant. At present we are nnot producing these cells locally but because of our expertise, excellent lab facilities and increased infra-structure consequent on this grant, we are being considered as potential producers if the initial results are promising 
 
Title mesenchymal stem cells (MSC) 
Description MSC developed from adherent cells grown from human bone marrow and used for the treatment of GvHD and graft failure in the context of stem cell transplantation 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact Offers an alternative therapy for treatment of complications of stem cell transplant 
 
Description Academic GMP 
Organisation Hannover Medical School
Department Department of Medicine
Country Germany 
Sector Academic/University 
PI Contribution The main objective of the research consortium is to generate new knowledge on the impact of advanced therapies regulations in the field of both academic sectors as well as on regulatory authorities and various stakeholders. Our role is in an advisory capacity, hence the limited funding, but we occupy an influential role in the project. In part because of the adverse impact of the U Clinical Trials Directive on academic led investogator trials we were anxious that the same did not occur in the provision of cellular therapy by academic institutions. We hope to present concrete and important suggestions to policy makers as to how the ATMP regulations are impacting on the academic sector
Collaborator Contribution We were invited to participate in an EU Framework 7 project entitled "The impact of regulation (EC) No 1394/2007 on the development of Advanced Therapy Medicinal Products (ATMPs): an academic perspective". The project brings together eight European groups considered to be expert in the academic production of cells for human use.
Impact Kickoff meeting in Septenber 2010. First milestones have not yet been reached
Start Year 2010
 
Description Banking of mesenchymal stem cells for the treatment of graft-versus-host disease 
Organisation NHS Blood and Transplant (NHSBT)
Country United Kingdom 
Sector Public 
PI Contribution We have initiated mesenchymal stem cell (MSC) expansions for clinical use in the country and treated a number of patients. Therefore, we will provide the guidelines and the expertise to enable the other NBS facilities to start MSC production. We have also developed the screenings to assess MSC potency
Collaborator Contribution NBS provides facilities to grow mesenchymal stem cells and the storage for banking frozen batches
Impact We have only recently established the collaboration and we are now in the position to apply for a large NIHR grant to test the feasibility of establishing a central collection of MSC batches and distribute them to the Clinical Centres for the treatment of patients with graft-versus-host disease. The collaboration involves different disciplines: Haematology, Immunology, Pediatrics.
Start Year 2010
 
Description Efficacy and Safety of Donor Lymphocytes Depleted of Alloreactive T-cells (ATIR™) in Patients Undergoing a Peripheral Blood Stem Cell Transplant From a Related, Haploidentical Donor 
Organisation University of Wurzburg
Department Department of Hematology and Transplantation
Country Germany 
Sector Academic/University 
PI Contribution we have been directly involved in the development of the clinical trial, including the laboratory aspects of the study.
Collaborator Contribution this collaboration has resulted in a multi-centre clinical trial of a novel haploidentical transplantation approach. We will study the effects of the administration of donor lymphocytes, selectively depleted of host alloreactive T-cells (through the ex-vivo use of TH9402 dye and light) to restore immunity more rapidly, with the aim of limiting the number of infections and infection-related deaths.
Impact The clinical trial is registered on the clinicaltrials.gov website NCT00967343. The trial opened for recruitment in September 2009 and 26 patients across Europe an north America have been recruited. A preliminary report of the data so far will be presented at the European Blood and Marrow Transplantation Meeting in Paris in April 2011.
Start Year 2008
 
Description Exploitation of the innate immune response in cancer and development of GMP grade Natural Killer cells for adoptive transfer in the treatment of hematological malignancies 
Organisation Imperial College London
Department Faculty of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We have successfully scaled up the production of GMP grade NK cells that can be generated from healthy donors and infused into patients following allogeneic stem cell transplantation to prevent or treat relapse. A phase 1 dose escalation study to assess the safety of this approach will open for recruitment soon.
Impact PMID: 20562327
Start Year 2010
 
Description ICiC 6 - Picinali - Both EARS training package (BEARS) to maximise hearing abilities in teenage bilateral cochlear implant users. 
Organisation Guy's and St Thomas' NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution support in writing grant application, coordination of early PPI stage, early development of prototypes and coordination in grant writing.
Collaborator Contribution Support in writing grant application, coordination in grant writing.
Impact Successful Stage 1 application to NIHR Programme Grants for Applied Research
Start Year 2017
 
Description ICiC 6 - Picinali - Both EARS training package (BEARS) to maximise hearing abilities in teenage bilateral cochlear implant users. 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution support in writing grant application, coordination of early PPI stage, early development of prototypes and coordination in grant writing.
Collaborator Contribution Support in writing grant application, coordination in grant writing.
Impact Successful Stage 1 application to NIHR Programme Grants for Applied Research
Start Year 2017
 
Description ICiC 6 - Picinali - Both EARS training package (BEARS) to maximise hearing abilities in teenage bilateral cochlear implant users. 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution support in writing grant application, coordination of early PPI stage, early development of prototypes and coordination in grant writing.
Collaborator Contribution Support in writing grant application, coordination in grant writing.
Impact Successful Stage 1 application to NIHR Programme Grants for Applied Research
Start Year 2017
 
Description ICiC 6 - Picinali - Both EARS training package (BEARS) to maximise hearing abilities in teenage bilateral cochlear implant users. 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution support in writing grant application, coordination of early PPI stage, early development of prototypes and coordination in grant writing.
Collaborator Contribution Support in writing grant application, coordination in grant writing.
Impact Successful Stage 1 application to NIHR Programme Grants for Applied Research
Start Year 2017
 
Description Mesenchymal stem cells and allogeneic keratinocytes for the treatment of skin wounds 
Organisation Imperial College Healthcare NHS Trust
Department Department of Plastic and Reconstructive Surgery
Country United Kingdom 
Sector Hospitals 
PI Contribution We are responsible for the cell preparations and provide them to test in the patients
Collaborator Contribution They test the safety and efficacy of combining MSC and allogeneic keratinocyte preparations on patients affected by slow healing skin wounds.
Impact The collaboration is at its early stage but we have already treated one compassionate case with some success. This will put us in the position to apply for a translational grant in the next three months. The collaboration includes different disciplines: Haematology, Immunology, Plastic Surgery
Start Year 2010
 
Description Mesenchymal stem cells for the treatment of multiple sclerosis: a phase II clinical trial 
Organisation Imperial College London
Department Division of Brain Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We will prepare the mesenchymal stem cells in our facility and assess some of the immunological parameters following the cell infusion
Collaborator Contribution They will test mesenchymal stem cells to improve patients with aggressive forms of multiple sclerosis by cinducting a phase II clinical trial
Impact We have submitted a grant (£500,000) to fund the costs of the trial including cell preparation and the assessment procedures. It has been shortlisted and is currently being considered in the final stage of the competition. The collaboration involves different disciplines: Haematology, Immunology, Neurology.
Start Year 2010
 
Description Production of GMP-grade mesenchymal stem cells using 3-D scaffolds in bioreactors: clinical safety and efficacy 
Organisation Karolinska University Hospital
Department Department of Hematology
Country Sweden 
Sector Hospitals 
PI Contribution We have initiated this collaboration with a view of bringing bioreactors into the clinical preparation of cell therapies. We will test their use and feasibility in GMP conditions and eventually prepare the cells to be delivered at the participating clinical Centres (Hammersmith, Stockholm, Budapest). We will also assess the therapeutic potency of the MSC thus generated using a number of assays developed at our Centre
Collaborator Contribution They provide bioreactors for growing mesenchymal stem cellsThey will contribute to test safety and efficacy of mesenchymal stem cells grown in bioreactors for the treatment of patients with severe graft-versus-host diseaseThey will contribute to test safety and efficacy of mesenchymal stem cells grown in bioreactors for the treatment of patients with severe graft-versus-host disease
Impact The collaboration has started very recently but we have submitted a large European grant (€ 5,000,000) to fund the initiative. If successful, this project will enable us to produce large numbers of MSC for clinical use and make them available to several Clinical Centres. The collaborations involves different disciplines: Haematology, Immunology, Tissue engineering
Start Year 2010
 
Description Production of GMP-grade mesenchymal stem cells using 3-D scaffolds in bioreactors: clinical safety and efficacy 
Organisation Semmelweiss University
Department Haematology
Country Hungary 
Sector Academic/University 
PI Contribution We have initiated this collaboration with a view of bringing bioreactors into the clinical preparation of cell therapies. We will test their use and feasibility in GMP conditions and eventually prepare the cells to be delivered at the participating clinical Centres (Hammersmith, Stockholm, Budapest). We will also assess the therapeutic potency of the MSC thus generated using a number of assays developed at our Centre
Collaborator Contribution They provide bioreactors for growing mesenchymal stem cellsThey will contribute to test safety and efficacy of mesenchymal stem cells grown in bioreactors for the treatment of patients with severe graft-versus-host diseaseThey will contribute to test safety and efficacy of mesenchymal stem cells grown in bioreactors for the treatment of patients with severe graft-versus-host disease
Impact The collaboration has started very recently but we have submitted a large European grant (€ 5,000,000) to fund the initiative. If successful, this project will enable us to produce large numbers of MSC for clinical use and make them available to several Clinical Centres. The collaborations involves different disciplines: Haematology, Immunology, Tissue engineering
Start Year 2010
 
Description Production of GMP-grade mesenchymal stem cells using 3-D scaffolds in bioreactors: clinical safety and efficacy 
Organisation University of Basel
Department Department of Biomedicine
Country Switzerland 
Sector Academic/University 
PI Contribution We have initiated this collaboration with a view of bringing bioreactors into the clinical preparation of cell therapies. We will test their use and feasibility in GMP conditions and eventually prepare the cells to be delivered at the participating clinical Centres (Hammersmith, Stockholm, Budapest). We will also assess the therapeutic potency of the MSC thus generated using a number of assays developed at our Centre
Collaborator Contribution They provide bioreactors for growing mesenchymal stem cellsThey will contribute to test safety and efficacy of mesenchymal stem cells grown in bioreactors for the treatment of patients with severe graft-versus-host diseaseThey will contribute to test safety and efficacy of mesenchymal stem cells grown in bioreactors for the treatment of patients with severe graft-versus-host disease
Impact The collaboration has started very recently but we have submitted a large European grant (€ 5,000,000) to fund the initiative. If successful, this project will enable us to produce large numbers of MSC for clinical use and make them available to several Clinical Centres. The collaborations involves different disciplines: Haematology, Immunology, Tissue engineering
Start Year 2010
 
Title Autologous anti-CMV specific T-cells 
Description Large scale prduction of autologous anti-CMV lymphocytes now achieved. Phase I/II trial protocol completed, ethics applications currently submitted. Fully funded through this grant 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2010
Development Status Under active development/distribution
Impact No impact as yet 
 
Title Mesenchymal stem cells for treatment of GvHD 
Description We are now growing MSC from most of stem cell transplant donors for use as third party donations for patients with life-threatening GvHD in a phase II clinical study. Fully funded throughthis grant 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2009
Development Status Actively seeking support
Impact Control of steroid refractory life threatening GvHD in 40% of sufferers 
 
Title NK cells 
Description NK cells are a subset of T-lymphocytes with potential anti-tumour effects. This activity is fully funded from this grant. Associated laboratory studies funded through Biomedical Research Centre grant 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2010
Development Status Under active development/distribution
Impact Too early to assess impact 
 
Description Local fund-raisers 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact We have a local fund-raising activity in the form of our own charity. Funds raised by these individuals actually built the building in which the GMP lab is housed and they also helped to fund the construction of the lab and its equipment. We regularly host established and new fund-raisers, (probably now more than 200), explaining the nature of stem cell transplantation, its potential in regenerative medicine and showing then around the laboratory

Continued highly successful local fund-raising for equipment, bridging money for staff etc
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Patient and Family Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact In April 2013 we wil host a patient and family day for 400 patiets and their carers who have been affected by transplant

We predict this will be much appreacited by patients but we will formally evaluate the day
Year(s) Of Engagement Activity 2012
 
Description Presentation to fund raisers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Poster Presentation
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Potential donors have been invited to visit the unit and discuss our owrk

Increased funding to our local charity
Year(s) Of Engagement Activity 2009,2010,2011,2012
 
Description Presentation to fund raisers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Presentation to 300 fund-raisers for Leukaemia and Lymphoma Society, explaining future and wider applications of stem cell transplant

Appreciation voiced by LLR staff and by fund-raisers themselves
Year(s) Of Engagement Activity 2010
 
Description school visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Twice a year we host a visit by 12 6th formers from local school (so total now about 70) who plan to read medicine or science at university, explaining to them the nature of stem cell transplant, its potential wider applications, its current use and its current limitations

Schools always express deep appreciation, 6th formers write up visits in school magazines recommending participation to other students. One school has sent us 12 students over the three years and all 12 have subsequently applied for medicine
Year(s) Of Engagement Activity 2008,2009,2010