Hurdles in therapy with regulatory T cells

Piotr Trzonkowski; Rosa Bacchetta; Manuela Battaglia; David Berglund; Hermann Richard Bohnenkamp; Anja ten Brinke; Andrew Bushell; Nathalie Cools; Edward K. Geissler; Silvia Gregori; S. Marieke van Ham; Catharien Hilkens; James A. Hutchinson; Giovanna Lombardi; J. Alejandro Madrigal; Natalia Marek-Trzonkowska; Eva M. Martinez-Caceres; Maria Grazia Roncarolo; Silvia Sanchez-Ramon; Aurore Saudemont; Birgit Sawitzki

doi:10.1126/scitranslmed.aaa7721

PerspectiveImmunology

Hurdles in therapy with regulatory T cells

Piotr Trzonkowski¹,*,†,
Rosa Bacchetta²,
Manuela Battaglia³,
David Berglund⁴,
Hermann Richard Bohnenkamp⁵,
Anja ten Brinke⁶,
Andrew Bushell⁷,
Nathalie Cools⁸,
Edward K. Geissler⁹,
Silvia Gregori¹⁰,
S. Marieke van Ham⁶,
Catharien Hilkens¹¹,
James A. Hutchinson¹²,
Giovanna Lombardi¹³,
J. Alejandro Madrigal¹⁴,
Natalia Marek-Trzonkowska¹⁵,
Eva M. Martinez-Caceres¹⁶,
Maria Grazia Roncarolo¹⁰,¹⁷,
Silvia Sanchez-Ramon¹⁸,
Aurore Saudemont¹⁴ and
Birgit Sawitzki¹⁹

¹Medical University of Gdansk, Department of Clinical Immunology and Transplantology, Debinki 7, 80-952 Gdansk, Poland.
²Department of Pediatric Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Standford, California, USA.
³Diabetes Research Institute (DRI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
⁴Uppsala University, Department of Immunology, Genetics and Pathology; Section of Clinical Immunology, Rudbeck Laboratory, 751 85 Uppsala, Sweden.
⁵Miltenyi Biotec GmbH, Clinical Business, Friedrich-Ebert-Straße 68, 51429 Bergisch Gladbach, Germany.
⁶Department of Immunopathology, Sanquin Blood Supply, Division Research, Plesmanlaan 125, 1066 CX Amsterdam, Netherland and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
⁷Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
⁸Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital (UZA), Wilrijkstraat 10, B-2650 Edegem, Belgium.
⁹Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg, Regensburg, Bavaria, 93053, Germany.
¹⁰San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹¹Institute of Cellular Medicine, Newcastle University NE2 4HH, UK.
¹²Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg, Regensburg, 93053, Bavaria, Germany.
¹³Medical Research Council (MRC) Centre in Transplantation, King^’s College London, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK.
¹⁴Anthony Nolan Research Institute, University College London (UCL) Royal Free Hospital Campus, 77c Fleet Road, London NW3 2QG, UK.
¹⁵Department of Family Medicine, Medical University of Gdańsk, Ul. Dębinki 2 80-210 Gdańsk, Poland.
¹⁶Immunology Division, Germans Trias i Pujol University Hospital. Campus Can Ruti. Department of Cellular Biology, Physiology, and Immunology, Universitat Autònoma Barcelona 08916, Badalona, Barcelona, Spain.
¹⁷Department of Pediatric Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, California, USA.
¹⁸Departamento de Inmunología Clínica, Hospital Clínico San Carlos, Calle Profesor Martín Lagos S/N, E- 28040 Madrid, Spain.
¹⁹AG Transplantationstoleranz, Charite Universitätsmedizin, Institut für Med. Imunologie, Augustenburgerplatz 1, 13353 Berlin, Germany.

^†All authors equally contributed to this work.

↵*Corresponding author. E-mail: ptrzon{at}gumed.edu.pl

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Science Translational Medicine 09 Sep 2015:
Vol. 7, Issue 304, pp. 304ps18
DOI: 10.1126/scitranslmed.aaa7721

Piotr Trzonkowski

1Medical University of Gdansk, Department of Clinical Immunology and Transplantology, Debinki 7, 80-952 Gdansk, Poland.

†All authors equally contributed to this work.

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For correspondence: ptrzon@gumed.edu.pl

Rosa Bacchetta

2Department of Pediatric Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Standford, California, USA.

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Manuela Battaglia

3Diabetes Research Institute (DRI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.

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David Berglund

4Uppsala University, Department of Immunology, Genetics and Pathology; Section of Clinical Immunology, Rudbeck Laboratory, 751 85 Uppsala, Sweden.

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Hermann Richard Bohnenkamp

5Miltenyi Biotec GmbH, Clinical Business, Friedrich-Ebert-Straße 68, 51429 Bergisch Gladbach, Germany.

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Anja ten Brinke

6Department of Immunopathology, Sanquin Blood Supply, Division Research, Plesmanlaan 125, 1066 CX Amsterdam, Netherland and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.

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Andrew Bushell

7Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.

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Nathalie Cools

8Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital (UZA), Wilrijkstraat 10, B-2650 Edegem, Belgium.

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Edward K. Geissler

9Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg, Regensburg, Bavaria, 93053, Germany.

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Silvia Gregori

10San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.

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S. Marieke van Ham

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Catharien Hilkens

11Institute of Cellular Medicine, Newcastle University NE2 4HH, UK.

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James A. Hutchinson

12Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg, Regensburg, 93053, Bavaria, Germany.

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Giovanna Lombardi

13Medical Research Council (MRC) Centre in Transplantation, King’s College London, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK.

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J. Alejandro Madrigal

14Anthony Nolan Research Institute, University College London (UCL) Royal Free Hospital Campus, 77c Fleet Road, London NW3 2QG, UK.

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Natalia Marek-Trzonkowska

15Department of Family Medicine, Medical University of Gdańsk, Ul. Dębinki 2 80-210 Gdańsk, Poland.

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Eva M. Martinez-Caceres

16Immunology Division, Germans Trias i Pujol University Hospital. Campus Can Ruti. Department of Cellular Biology, Physiology, and Immunology, Universitat Autònoma Barcelona 08916, Badalona, Barcelona, Spain.

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Maria Grazia Roncarolo

10San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.

17Department of Pediatric Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, California, USA.

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Silvia Sanchez-Ramon

18Departamento de Inmunología Clínica, Hospital Clínico San Carlos, Calle Profesor Martín Lagos S/N, E- 28040 Madrid, Spain.

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Aurore Saudemont

14Anthony Nolan Research Institute, University College London (UCL) Royal Free Hospital Campus, 77c Fleet Road, London NW3 2QG, UK.

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Birgit Sawitzki

19AG Transplantationstoleranz, Charite Universitätsmedizin, Institut für Med. Imunologie, Augustenburgerplatz 1, 13353 Berlin, Germany.

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Abstract

Improper activation of the immune system contributes to a variety of clinical conditions, including autoimmune and allergic diseases as well as solid organ and bone marrow transplantation. One approach to counteract this activation is through adoptive therapy with regulatory T cells (T_regs). Efforts to manufacture these cells have led to good maunfacturing practice–compliant protocols, and T_reg products are entering early clinical trials. Here, we report the stance of the European Union Cooperation in Science and Technology Action BM1305, “Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies—A FACTT,” which identifies hurdles hindering T_reg clinical applications in Europe and provides possible solutions.

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Hurdles in therapy with regulatory T cells

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Science Translational Medicine

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