Immunobiology

Projects

Current Projects:

AlloStem - A World-Wide Joint Venture that will Change the Treatment of Haematopoietic Malignant Disorders

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An exciting new research programme, AlloStem, funded by the European Commission and led by Professor Alejandro Madrigal (Scientific Director of The Anthony Nolan Trust), hopes to transform the treatment of leukaemia and to significantly increase the chance of survival for many patients. After a two-year-long application process and strong competition from Europe's most eminent research groups, a grant of eight million euros from the European Commission (EC) has enabled the creation of 'AlloStem'; a consortium of leading immunologists and clinical scientists dedicated to improving cancer therapies. This grant represents a watershed in European Union medical research funding and will be the largest grant the EC has ever awarded to an immunotherapy programme.

There have been important advances in the treatment of leukaemia and other haematological malignancies over the last 30 years, including improvements in chemotherapy and the use of other agents such as interferon and engineered antibodies targeting tumour-associated motifs. Despite these advances, haematopoietic stem cell transplantation (HSCT) remains the only therapy that can result in long-term disease free survival for many patients; especially those patients who suffer a relapse following initial chemotherapy. However, at present, allogeneic HSCT can carry some post-transplant complications, mainly due to recurrence or progression of the primary disease, graft versus host disease (GvHD) and infections due to immuno-protection deficiency. The AlloStem project aims to increase the number of patients that could benefit from HSCT with the use of immunotherapy. This will involve allogeneic HSCT with subsequent delivery of specific immune effector cells isolated from the donors and then expanded. Hence, the scientific and technological objectives of this project are to develop new immunotherapy strategies based on the prediction and modulation of the immune response. The outcomes hoped-for are to:

1. reduce the risk of GvHD
2. generate selective anti-tumour immune responses
3. provide protective immunity against opportunistic infections
4. extend applicability to a larger proportion of patients

AlloStem is a joint research venture focussing on the development of new technologies in the field of stem cell transplantation and the transformation of these new technologies into clinical applications. The teams participating in this project include 29 centres-of-excellence from 13 different countries across the world. With the addition of a group of Associate Partners, AlloStem represents over 50 scientific and clinical research groups from 19 different countries. These groups comprise of leading clinicians and scientists in the fields of stem cell biology, immunogenetics, transplantation, cell processing and immunotherapy. With the wider implications of the new therapies in mind, AlloStem has incorporated advisory committees of experts in law, ethics, social science and policy regulations, together with representatives of patients and donor organisations. This represents an interactive and complementary network that, unique to this field, combines the competence and the technical skills to achieve its ambitious goals.

The groups involved have excellent performance-related backgrounds in trans-European collaborative studies and have delivered significant clinical and scientific advances over a period of more than 20 years. For example, Professors Fred Falkenburg and Els Goulmy of the Leiden University Medical Centre have made important contributions in demonstrating how donor cells, specific for genetic differences between donor and recipient, can be effective in eliminating leukaemia. Prof. Manuel Fernandez of the Hospital Puerta de Hierro (Madrid) is a leading expert in the use of different sources of stem cells for out-bone-marrow transplants. Prof. Herman Einsele (Tubingen) is, likewise, a leading expert in applying the techniques of immunotherapy to common viral diseases observed in transplant recipients and together with Prof. Franco Locatelli (Pavia) is developing therapies for the treatment of fungal diseases.

List of Partners:

Co-ordinator: Prof. Alejandro MADRIGAL United Kingdom

WP Co-ordinators:

• Prof. Fred FALKENBURG Netherlands
• Prof. Hermann EINSELE Germany
• Prof. Manuel FERNANDEZ Spain

Partners:

List of Associate Partners:

• Prof. Jane Apperley Department of Haematology, Imperial College London, UK
• Dr. Rafael Arguello Director of Postgraduate Studies and Research, University Autonoma of Coahuila, Mexico
• Dr. Samir Agrawal Senior Lecturer & Hon. Consultant in Haematology, St. Bartholomew's & London Hospital, Queen Mary College, University of London, London, UK
• Prof. John Barrett Head, Haematology Immunotherapy Service, Haematology Branch, National Institutes of Health, Maryland, USA
• Dr. Juan Besalduch Haematology Service, Hospital University Son Dureta, Palma de Mallorca, Spain
• Prof. Rainer Blasczyk Head, Institute for Transfusion Medicine, Hannover, Germany
• Dr. Chiara Bonini Cancer Immunotherapy and Gene Therapy Program, BMT Unit, Milan. Italy
• Dr. Agnès Buzyn Head, Tumour, Immunity and Immunotherapy Group, Department of Immunology and Adult Haematology Service, Paris, France
• Dr. Richard Clark Head, Department of Haematology, Royal Liverpool University Hospital, Liverpool, UK
• Dr. Octavio Campollo Health and Science Consultant, Guadalajara, Mexico
• Prof. Anne Dickinson Head, Marrow Transplant Biology, Royal Victoria Infirmary, Newcastle upon Tyne, UK
• Prof. Javier Garcia Conde Valencia, Spain
• Dr. Sergio Giralt Head, Dept. of Haematology, MD Anderson Cancer Center, Houston, Texas
• Dr. Oscar Gonzalez Ramella Guadalajar Jalisco, Mexico
• Prof. Alberto Grañena Head, Haematological Division, Catalan Institute of Oncology, Barcelona, Spain
• Dr. Mary Horowitz Scientific Director, International Bone Marrow Transplant Registry. Medical College of Wisconsin Milwaukee, USA
• Dr. Anita Hristova-Dimceva, Head, Histocompatibility Laboratory, Institute of Blood Transfusion, Medical Faculty, University of St. Cyrilus and Methodius, Skopje, Macedonia
• Prof. Han-Jochem Kolb Ludwig-Maximilians-University, Munich, Germany
• Dr. Gustavo Kusminsky Head, Department of Haematology, Hospital Austral, Buenos Aires, Argentina
• Prof. Piot Laidler Institute of Medical Boichemistry, Jagellonian University Medical College, Krakow, Poland
• Dr. Angel Leon Lara Head, Department of Haematology, SAS Hospital, Cadiz Jerez de la Fontera, Spain
• Dr. Susanne Matthes-Martin Stem Cell Transplantation, St. Anna Children's Hospital, Children's Cancer Research Institute (CCRI), Vienna, Austria
• Prof. Derek Middleton Head, Histocompatibility & Immunogenetics Laboratory, City Hospital, Belfast, Northern Ireland
• Dr. Jeffrey Molldrem Assistant Professor, Immunotherapy Group, M.D. Anderson Cancer Centre, Houston, Texas, USA
• Prof. David Moss Dept. of Crystallography, Birkbeck College, London Prof. Ghulam Mufti Professor of Haemato-Oncology. King's College Hospital, London, UK
• Prof. Arnon Nagler Director, Bone Marrow Transplantation Department and Cord Blood Bank, The Chaim Sheba Medical Center, Hashomer, Israel
• Dr. Cristina Navarette National Head of H&I for NBS, North London Blood Transfusion Centre, Colindale, London, UK
• Dr. Dietger Niederweiser Division of Hematology/Oncology, Dept. of Internal Medicine, University Hospital Leipzig, Germany
• Dr. Roberto Ovilla Head, Haematology and Oncology Department; Chief, Bone Marrow Transplantation Unit, Hospital Angeles de las Lomas, Mexico City, Mexico
• Dr Julia Palma Assistant Professor of Pediatrics and Head of the Bone Marrow transplantation Unit, Hospital Luis Calvo Mackenna, University of Chile School of Medicine, Santiago, Chile
• Prof. Graham Pawelec Head of TATI Centre for Medical Research, Tubingen, Germany
• Prof. Grant Prentice Head, Transplantation Department, The London Clinic, London, UK
• Prof. Felipe Prosper Associate Professor of Haematology and Cell Therapy, Clinical University of Navarra, Pamplona, Spain
• Prof. Pablo Rubinstein Cord Blood Bank, New York, USA
• Dr. Jonathan Schneck Associate Professor of Pathology, The Johns Hopkins University School of Medicine, Baltimore, USA
• Dr. Antonij Slavcev Head of Deparment of Immunogenetics, IKEM, Czech Republic
• Prof. Shimon Slavin Chair, Dept. of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel
• Dr. Rüdiger Sorg Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Düsseldorf, Germany
• Dr.Cesar Trigueros Inbiomed Foundation, San Sebastian, Spain
• Prof. Herman Waldmann Professor of Pathology, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK

Alejandro Madrigal
IWP Chairman
madrigal@rfc.ucl.ac.uk