MERLIN Press release: University of Birmingham trials a new stromal cell immunotherapy for chronic liver disease

 The University of Birmingham has launched a trial which could lead to a ground-breaking new way of treating people with two types of chronic liver disease. 

Up to 56 patients are being recruited to take part in the MERLIN trial, which will investigate the safety and efficacy of a new cellular immunotherapy in patients with either Primary Sclerosing Cholangitis (PSC) or Autoimmune Hepatitis (AIH). 

Both PSC and AIH involve inflammation of the bile ducts, which can result in significant liver damage and many of those affected end up needing a liver transplant. Current options for treating PSC and AIH are limited. 

The new cell therapy being trialled is a single infusion of specially selected mesenchymal stromal cells (MSCs) which will be administered to participants. The first patient has recently received the cells at Queen Elizabeth Hospital, Birmingham, which is run by University Hospitals Birmingham NHS Foundation Trust. Further clinical centres at John Radcliffe Hospital, Oxford, and Queen’s Medical Centre, Nottingham, are due to open later this year. It is anticipated that the trial will run until autumn next year. The trial is sponsored by the University of Birmingham and coordinated by the Inflammation–Advanced and Cellular Therapy team at Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham. The trial is funded by the EU FP7 Project MERLIN (Grant agreement no: 602363) and NIHR Birmingham Biomedical Research Centre. 

Chief Investigator Professor Phil Newsome, of the University of Birmingham’s Institute of Immunology and Immunotherapy and Deputy Director of NIHR Birmingham Biomedical Research Centre, said: “I am very excited about the potential benefits of this treatment for patients with PSC and AIH. 

“There is good evidence that the selected cells being used in this new immunotherapy can reduce liver inflammation and improve liver function. 

“The initial aims are to prove the safety and efficacy of the treatment and it could possibly be used in future trials to treat other immune and inflammatory diseases. 

“We are indebted to the whole MERLIN team who worked so hard to bring about this trial and patients who have given up their time to be considered for this trial.” 

The cell product being administered in the MERLIN trial is called ORBCEL-Cand was discovered by Dr. Steve Elliman at Orbsen Therapeutics in Ireland. 

Steve Elliman, Chief Scientific Officer at Orbsen Therapeutics, said: “We are optimistic taking the ORBCEL-C immunotherapy to the clinic as a solution to slow or stop these chronic autoimmune liver diseases. 2 

“On behalf of Orbsen, we are privileged to be engaged with some of the European Union’s leading researchers and institutions in the MERLIN program.” 

ORBCEL-C is being manufactured for the trial by NHS Blood and Transplant in Birmingham. The trial is the culmination of the MERLIN Project, which also involved researchers from the University of Padua, Erasmus Medical Centre and BioInVision Inc. 

Anyone aged over 18 with PSC or AIH who is interested in joining the trial can contact the trial management team in Birmingham at merlin@trials.bham.ac.uk for more information. Specific inclusion criteria must be satisfied before admission to the trial. 

Depending on the results achieved a further trial with a larger patient cohort may be warranted. 

Ends 

For more information please contact Emma McKinney, Communications Manager (Health Sciences), University of Birmingham, Email: e.j.mckinney@bham.ac.uk or tel: +44 (0) 121 414 6681, or contact the press office on +44 (0) 7789 921 165 or pressoffice@contacts.bham.ac.uk 

MERLIN Final Flyer published

Would you like to read a capsule summary of what the MERLIN project has accomplished? Well, please download and share the MERLIN Final Flyer here.

http://fp7merlin.eu/wp-content/uploads/2019/03/Merlin-Final-Flyer-screen.pdf

MERLIN MSC Researcher Dr Samantha de Witte defends her PhD dissertation

On Tuesday, November 20, 2018, Dr Samantha de Witte successfully defended her PhD. research at Erasmus Medical Center, Rotterdam, NL. The title of Dr de Witte’s dissertation was “Probing the immunomodulatory potential of mesenchymal stromal cells”.

MERLIN Coordinator Prof Phil Newsome, University of Birmingham, UK was one of Samantha’s external examiners.

Congratulations, Samantha!

           

Roberta Angioni, U of Padova awarded for outstanding Bright Spark presentation at ECI meeting

MERLIN PhD student Roberta Angioni of the Università degli Studi di Padova was selected for a “Bright Spark” presentation during the 5th European Congress of Immunology (ECI). The ECI meeting was held in Amsterdam on September 2-5, 2018.

Roberta remarks: “With my great pleasure, I was awarded with the “EFIS-Biolegend Bright Sparks Award for a presentation judged outstanding” for my presentation entitled “Extracellular Vesicles derived from licensed Mesenchymal Stem Cells: a tunable approach to regulate inflammatory angiogenesis (R. Angioni, S. Herkenne, C. Liboni, R. Sanchez-Rodriguez, B. Calì, G. Borile, A. Viola, Padova, Italy)”.

Erasmus MC Mentor-Mentee team wins at Congress of the Transplantation Society

Erasmus Medical Center PhD student Jesus Sierra presented Merlin data at the Congress of the Transplantation Society in Madrid in July 2018. The title of Jesus’ talk was:  Monocytic cells phagocytose therapeutic mesenchymal stem cells, which induces polarization, relocation and immune regulation. Jesus Sierra in conjunction with Martin Hoogdujin, his mentor claimed the mentor-mentee award at the 27th International Congress of The Transplantation Society.  This year’s meeting was held in Madrid, Spain from June 30 to July 5, 2018.

Pictured below from left to right: Martin Hoogduijn, Erasmus Medical Center, Rotterdam, Marlies Reinders, President of the Dutch Transplantation Society, and Jesus Sierra, presenter and PhD student.

MERLIN publishes in Cytotherapy

The MERLIN study “Epigenetic changes in umbilical cord mesenchymal stromal cells upon stimulation and culture expansion” has been recently published in Cytotherapy The Journal of Cell Therapy. The body of research by Samantha F.H. de Witte1, Fleur S. Peters1, Ana Merino1, Sander S. Korevaar1, Joyce B.J. van Meurs2, Lisa O’Flynn3, Steve J. Elliman3, Philip N. Newsome46, Karin Boer1, Carla C. Baan1 and Martin J. Hoogduijnwas accepted for publication on May 8, 2018. Cytotherapy is the Official Journal of the International Society for Cellular Therapy (ISCT)

Abstract: Mesenchymal stromal cells (MSCs) are studied for their immunotherapeutic potential. Prior to therapeutic use, MSCs are culture expanded to obtain the required cell numbers and, to improve their efficacy, MSCs may be primed in vitro. Culture expansion and priming induce phenotypical and functional changes in MSCs and thus standardisation and quality control measurements come in need. We investigated the impact of priming and culturing on MSC DNA methylation and examined the use of epigenetic profiling as a quality control tool.

Read about the roles of the partner organizations within MERLIN here.

doi: https://doi.org/10.1016/j.jcyt.2018.05.005 [Epub ahead of print]

Published on June 19, 2018.

Find the link to the paper here.

1Nephrology and Transplantation, 2Endocrinology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands; 3Orbsen Therapeutics Ltd., Galway, Ireland; 4National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. 5Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham. 6Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

 

MERLIN trial attracts attention at Bioprocessing and Advanced Cellular Therapies Congress 2018

 

Head of Process Development at Orbsen Therapeutics, Limited, Dr Lisa O’ Flynn attended the 3rd Annual Bioprocessing and Advanced Cellular Therapies Congress in Frankfurt, Germany. The meeting was held on the 29th-30th of May 2018. Lisa gave an oral presentation entitled ” CD362 to ORBCEL: the rapid development of a novel stromal cell therapy ” wherein the MERLIN clinical trial was highlighted.

Immunomodulation By Therapeutic MSC Is Triggered Through Phagocytosis of MSC By Monocytic Cells

A new MERLIN publication led by our team at Erasmus MC in Rotterdam, NL appeared in the journal Stem Cells on 17 January 2018. Authors of this paper are: Samantha F H de Witte , Franka Luk, Jesus M Sierra Parraga, Madhu Gargesha, Ana Merino, Sander S Korevaar, Anusha S Shankar, Lisa O’Flynn, Steve J Elliman, Debashish Roy , Michiel G H Betjes, Philip N Newsome, Carla C Baan, Martin J Hoogduijn.

This important study demonstrates that infused MSC are rapidly phagocytosed by monocytes, which subsequently migrate from the lungs to other body sites. Phagocytosis of ucMSC induces phenotypical and functional changes in monocytes, which subsequently modulate cells of the adaptive immune system. It can be concluded that monocytes play a crucial role in mediating, distributing, and transferring the immunomodulatory effect of MSC.

Visit our Publications page for more information on this and other MERLIN publications.

 

Merlin team meet in Padua

The Merlin partners met in Padua on 22 and 23 January for our most recent plenary. The team heard updates from workstreams across the project and discussed the reports to be submitted to the EU by the end of January. MSC manufacture and plans for the clinical trial were also a key focus. An exploitation workshop was held where future exploitation plans were considered. Many thanks to UNIPD for hosting such a successful meeting in such a wonderful location!

 

S. de Witte, Erasmus MC presents MERLIN findings in 2017

S. de Witte of Erasmus University Medical Center in Rotterdam took to the road in 2017 to present MERLIN results at five conferences in Belgium, The Netherlands and Spain:

· Erasmus MC, Science days of the Department of Internal Medicine, Antwerp
Poster: IMPACT OF CULTURE EXPANSION AND INFLAMMATORY CYTOKINE CHALLENGE ON DNA METHYLATION PROFILES IN MSC

· BOOT conference, Dutch Transplantation Society, Groningen
Presentation 1: Ageing of bone marrow and umbilical cord-derived MSC during culture expansion
Presentation 2: In vivo tracking of live and dead mesenchymal stromal cells

· MOLMED day, Erasmus MC molecular medicine, Rotterdam
Poster: IMPACT OF CULTURE EXPANSION AND INFLAMMATORY CYTOKINE CHALLENGE ON DNA METHYLATION PROFILES IN MSC

· European Society for Organ Transplantation (ESOT), Barcelona
Presentation 1: Impact of culture expansion and inflammatory cytokine challenge on DNA methylation profiles in MSC
Presentation 2: Tracking and fate of umbilical cord-derived MSC after intravenous infusion in mice (presented by F. Luk)

· European Hematology Association (EHA), EHA-SWG Scientific Meeting on Shaping the Future of Mesenchymal Stromal Cells Therapy, Amsterdam
Presentation: Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells

After six conference talks and poster presentations, she remarked, ”It was nice to connect with the experts in the field”.