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

Proteomic analysis of the secretome of human bone marrow-derived MSCs

MERLIN team at the Universitá degli Studi di Padova publish “Proteomic analysis of the secretome of human bone marrow-derived mesenchymal stem cells primed by pro-inflammatory cytokines” in the Journal of Proteomics, 21July 2017

Congratulations to all authors: Elisa Maffioli, Simona Nonnis, Roberta Angioni, Fabiana Santagata, Bianca Calí, Lucia Zanotti, Armando Negri, Antonella Viola, Gabriella Tedeschi.

In summary, the secretion of a broad range of bioactive molecules is believed to be the main mechanism by which mesenchymal stem cells (MSC) exert specific therapeutic effects. MSC are very versatile and respond to specific environments by producing and releasing a variety of effector molecules. To the best of our knowledge this is the first study aimed at describing the secretome of human MSC primed using a mixture of cytokines, to mimic pro-inflammatory conditions encountered in vivo, by a quantitative high-resolution mass spectrometry based approach. The main output of the study concerns the identification of a list of specific proteins involved in inflammation and angiogenesis which are overrepresented in stimulated MSC secretome.
This study found that pro-inflammatory cytokines have a strong impact on the secretome of human bone marrow-derived MSC and that the large majority of cytokine-induced proteins are involved in inflammation and/or angiogenesis.
Overall, these studies represent key steps necessary to characterize the different biology of MSC in the two organisms and design successful pre- clinical experiments as well as clinical trials. The full publication is available at: https://doi.org/10.1016/j.jprot.2017.07.012

Merlin Article Published on Optimisation of MSC

A new Merlin article on Optimisation of MSC has just been published in Stem Cell Research and Therapy. The piece is entitled “Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease” and was lead by Samantha de Witte from Erasmus MC in the Netherlands. The paper is open access (Stem Cell Research & Therapy 20178:140 DOI: 10.1186/s13287-017-0590-6) and can be downloaded here. 

Congratulations to all the authors (Samantha F. H. de Witte; Ana M. Merino, Marcella Franquesa, Tanja Strini, Johanna A. A. van Zoggel, Sander S. Korevaar, Franka Luk, Madhu Gargesha, Lisa O’Flynn, Debashish Roy, Steve J. Elliman, Philip N. Newsome, Carla C. Baan and Martin J. Hoogduijn).

Merlin Meet in Rotterdam

The Merlin team had a very successful plenary in Rotterdam on 10 and 11 May. Updates were presented on each WP. MSC production and preparation for the upcoming trial were naturally a key focus at this stage of the project. Publications and plans for future work were also discussed. Many thanks to EMC for hosting and to all the partners for their input into a very productive and enjoyable meeting!

MERLIN article for publication in Cytotherapy

A Merlin paper on the impact of long-term in vitro expansion on MSCs has been accepted for publication in Cytotherapy. The article is entitled “Aging of bone marrow and umbilical cord–derived mesenchymal stromal cells during expansion” (by Samantha de Witte (pictured above), Eleonora E. Lambert, Ana Merino, Tanja Strini, Hannie J.C.W. Douben, Lisa O’Flynn, Steve J. Elliman, Annelies J.E.M.M. de Klein, Philip N. Newsome, Carla C. Baan and Martin J. Hoogduijn). The corrected proof is now available on line: here. Congratulations to the authors!

Merlin Newsletter Autumn 2016

newsletter-autumn-2016

The project team are pleased to issue the first Merlin Newsletter (for Autumn 2016). You can access the newsletter above. Contents in this edition include:

  • MERLIN at a Glance – a reminder of the project’s key aims and objectives.
  • Read All About it – details of some of our recent publications.
  • At the Lectern – some key presentations delivered by the MERLIN team.
  • Progress and Next Steps – where to find progress updates and a look at next steps.
  • Meet the Team – the partners behind the project.

 

 

Merlin Plenary Meeting in Galway

Merlin partner Orbsen hosted the latest Merlin plenary, held in Galway on 17 and 18 October. The meeting was very productive and included updates from all scientific work packages, aswell as reviews of IP, dissemination/exploitation and use of resources. Break-out sessions were also organised so that PIs and postdocs could collaborate in smaller groups. The team looks forward to delivering the work plan agreed for the weeks and months ahead.

Merlin article published in “Leukemia”

An article published by Merlin researchers from UNIPD has recently been published in the “Leukemia” journal. The piece is entitled  “Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1(Author(s): Zanotti L, Angioni R, Calì B, Soldani C, Ploia C, Moalli F, Gargesha M, D’Amico G, Elliman S, Tedeschi G, Maffioli E, Negri A, Zacchigna S, Sarukhan A, Stein JV, Viola A) and appears in the May issue. The article deals with the impact of MSC on immunity and inflammation and identifies TIMP-1 as a novel biomarker for MSC-based therapy. You can access the article here.

Merlin Report for Year 2

In March 2015 we issued a report summarising the work undertaken during the first year of the project. Our second report, for year 2 of Merlin is now available. You can access the year 2 report  below.

MERLIN Report Year 2