ABSTRACT
Cellular immunotherapy consists in using the cells of the immune system as a therapeutic weapon. In this constantly evolving field, the therapeutic strategies developed at the University Hospital of Liege are hematopoietic stem cell transplantation, mesenchymal stromal cells and targeted therapy with CAR-T cells (Chimeric Antigen Receptor T cells). The first two modalities represent a form of non-targeted cell therapy that has been developed over the past decades. While hematopoietic stem cell transplantation is established as the reference treatment for many hematological diseases, mesenchymal stromal cells are still under investigation in various pathologies (notably Crohn's disease, organ transplantation, COVID-19 and pulmonary fibrosis). By contrast, CAR-T cells represent a recently developed and extremely promising targeted immunotherapy. This therapeutic approach has already revolutionized the treatment of B-cell lymphopathies, and has the potential to do the same for many other diseases in the near future.
L'immunothérapie cellulaire consiste en l'utilisation de cellules du système immunitaire comme arme thérapeutique. Dans ce domaine en évolution constante, les stratégies thérapeutiques développées au CHU de Liège sont la greffe de cellules souches hématopoïétiques, les cellules stromales mésenchymateuses et la thérapie ciblée par cellules CAR-T («Chimeric Antigen Receptor T cells¼). Les deux premières approches représentent une forme de thérapie cellulaire non ciblée, développées depuis de nombreuses années. Si la greffe de cellules souches hématopoïétiques est établie comme le traitement de référence de nombreuses hémopathies, les cellules stromales mésenchymateuses sont, quant à elles, toujours à l'étude dans diverses pathologies (notamment maladie de Crohn, transplantation d'organes, COVID-19 et fibrose pulmonaire). À l'opposé, les cellules CAR-T représentent une immunothérapie ciblée, développée récemment et extrêmement prometteuse. Cette modalité thérapeutique a déjà révolutionné le traitement des lymphopathies B, et elle possède le potentiel d'en faire de même pour de nombreuses autres pathologies dans un avenir proche.
Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Receptors, Chimeric Antigen , COVID-19/therapy , Hospitals , Humans , ImmunotherapyABSTRACT
BACKGROUND: Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair. AIM: To review the current data on mesenchymal stromal cell therapy in IBD. METHOD: We searched PubMed and 'ClinicalTrials.gov' databases using the terms 'mesenchymal stromal cells', 'mesenchymal stem cell transplantation', 'inflammatory bowel diseases', 'Crohn disease' and 'colitis, ulcerative'. Additional publications were identified from individual article reference lists. RESULTS: MSCs include inhibition of Th1/Th17 lymphocytes and recruitment of regulatory T lymphocytes, induction of antigen-presenting cells into a regulatory-like profile, and stimulation of epithelial cell differentiation and proliferation. More than 200 patients with refractory fistulas have been treated with local injections of MSCs, resulting in complete response in more than half, and in overall response in approximately two thirds of patients. In refractory luminal Crohn's disease, 49 cases of systemic MSC infusions have been reported, while trials with autologous MSCs resulted in mitigated responses, studies using allogeneic MSCs were promising, with around 60% of patients experiencing a response and around 40% achieving clinical remission. CONCLUSIONS: Mesenchymal stromal cells might represent a promising therapy for IBD, especially for Crohn's disease. There remain many unsolved questions concerning the optimal origin and source of mesenchymal stromal cells, dosage and modalities of administration. Moreover, mesenchymal stromal cells still need to prove their effectiveness compared with conventional treatments in randomised controlled trials.
Subject(s)
Inflammatory Bowel Diseases/therapy , Mesenchymal Stem Cell Transplantation , Animals , Colon/physiology , Humans , Inflammatory Bowel Diseases/immunology , Mesenchymal Stem Cells/immunology , RegenerationABSTRACT
Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of isehemic injury, and for their potential properties of tissue or organ reconstruction. Over the last few years, the potential role of MSC in organ transplantation has been studied both in vitro and in vivo, and their properties make them an ideal potential cell therapy after solid organ transplantation. A prospective, controlled, phase 1-2 study has been initiated at the CHU of Liege, Belgium. This study assesses the potential risks and benefits of MSC infusion after liver or kidney transplantation. Even if the preliminary results of this study look promising, solely a prospective, randomized, large scale, phase 3 study will allow the clinical confirmation of the theoretical benefits of MSC in solid organ transplantation.
