- Gene therapy for severe combined immunodeficiencyMarina Cavazzana-Calvo
Département de Biothérapie, Hopital Necker Enfants Malades, 75015 Paris, France
Annu Rev Med 56:585-602. 2005..This review discusses recent developments in SCID identification and treatment...
- Efficacy of gene therapy for SCID is being confirmedMarina Cavazzana-Calvo
, , 75015 Paris, France
Lancet 364:2155-6. 2004
- Gene transfer for activation of CMV specific T cellsIsabelle Andre-Schmutz
INSERM U429 I A S, M C C, Hopital Necker Enfants Malades, Paris, France
Hum Immunol 65:565-70. 2004..The protocols as well as the preclinical and clinical results obtained in the field of anti-CMV immunotherapy using gene transfer are reported and discussed...
- Gene therapy of RAG-2-/- mice: sustained correction of the immunodeficiencyFrank Yates
Institut National de la Santé et de la Recherche Médicale INSERM U429, Hopital Necker Enfants Malades, Paris, France
Blood 100:3942-9. 2002..Altogether, this study demonstrates the efficiency of ex vivo RAG-2 gene transfer in HSCs to correct the immune deficiency of RAG-2-/- mice, constituting a significant step toward clinical application...
- [Human hematopoiesis: from CD34 cells to T lymphocytes]Marina Cavazzana-Calvo
Département de Biothérapie, Hopital Necker Enfants Malades, Inserm U768, 149, rue de Sevres, 75015 Paris, France
Med Sci (Paris) 23:151-9. 2007....
- Immune reconstitution after haematopoietic stem cell transplantation: obstacles and anticipated progressMarina Cavazzana-Calvo
Assistance Publique Hopitaux de Paris AP HP, Department of Biotherapy, Hopital Necker Enfants Malades, Paris, France
Curr Opin Immunol 21:544-8. 2009..If these objectives could be achieved, the haploidentical procedure would become more readily available to patients affected by acquired or inherited disorders of the haematopoietic system...
- Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cellsFatine Benjelloun
Institut National de la Santé et de la Recherche INSERM, U768, Universite Paris Descartes, Hopital Necker Enfants Malades, Paris, France
Mol Ther 16:1490-9. 2008..As a whole, our work provides a basis for supporting the gene therapy approach in Artemis-deficient SCID...
- Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in ArtemisDespina Moshous
Unité Développement Normal et Pathologique du Système Immunitaire, Institut National de la Santé et de la Recherche Médicale INSERM U429, Hopital Necker Enfants Malades, Paris, France
J Clin Invest 111:381-7. 2003..This syndrome emphasizes the role of Artemis in the NHEJ pathway of DNA repair and suggests that other, yet ill-defined, conditions associating immunodeficiency and lymphoma could be caused by mutations in genes encoding NHEJ factors...
- Severe combined immunodeficiency. A model disease for molecular immunology and therapyAlain Fischer
INSERM U429, Hopital Necker Enfants Malades, Paris, France
Immunol Rev 203:98-109. 2005..SCID is thus a disease model for experimental therapy in the hematopoietic system...
- Medical perspectives of adults and embryonic stem cellsMarina Cavazzana-Calvo
INSERM, Unite 429, Hopital Necker, 149, rue de Sevres, 75015 Paris, France
C R Biol 325:1053-8. 2002..We have tried here to summarise the advances in this field and to discuss the limits of these biological data...
- IL-7 effect on immunological reconstitution after HSCT depends on MHC incompatibilityIsabelle Andre-Schmutz
INSERM U 429, Hopital Necker Enfants Malades, Paris, France
Br J Haematol 126:844-51. 2004....
- Gene therapy of X-linked severe combined immunodeficiencyMarina Cavazzana-Calvo
INSERM U429, Hopital Necker Enfants Malades, Paris, France
Curr Opin Allergy Clin Immunol 2:507-9. 2002..Definitive conclusions cannot be thrown due to the limited number of gene therapy-treated patients and their relatively short follow-up...
- Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1Salima Hacein-Bey-Abina
Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
J Clin Invest 118:3132-42. 2008..Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer...
- Gene therapy of X-linked severe combined immunodeficiencySalima Hacein-Bey-Abina
Gene and Cell Therapy Unit, , , Paris, France
Methods Mol Biol 215:247-59. 2003
- A human postnatal lymphoid progenitor capable of circulating and seeding the thymusEmmanuelle M Six
Institut National de la Sante et de la Recherche Medicale INSERM, U768, 75015 Paris, France
J Exp Med 204:3085-93. 2007..Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus...
- Characterization of antigen-specific repertoire diversity following in vitro restimulation by a recombinant adenovirus expressing human cytomegalovirus pp65Yamina Hamel
INSERM U429, , , F-75743 Paris Cedex 15, France
Eur J Immunol 33:760-8. 2003..Altogether, these results suggest that the use of RAdpp65 to induce CMV- and adenovirus-specific CTL maybe appropriate for immunotherapy...
- Advances in adoptive immunotherapy to accelerate T-cellular immune reconstitution after HLA-incompatible hematopoietic stem cell transplantationChristian Reimann
Institut National de la Sante et de la Recherche Medicale INSERM, Département de Biothérapie, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris, and Université Paris Descartes 75015 Paris, France
Immunotherapy 2:481-96. 2010..The present article will provide a brief summary of recent advances in the field of allodepletion and adoptive transfer of pathogen-specific T cells and a detailed discussion of strategies for enhancing thymopoiesis in vivo...
- Gene therapy for immunodeficiency diseasesAlain Fischer
INSERM U 429, Hopital Necker Enfants Malades, Paris, France
Semin Hematol 41:272-8. 2004..New advances in the technology of gene transfer should further promote gene therapy as a safe and effective therapeutic strategy of immunodeficiency diseases...
- Gene therapy of severe combined immunodeficienciesAlain Fischer
INSERM U429, Hopital Necker, 149 rue de Sevres, 75015 Paris, France
Nat Rev Immunol 2:615-21. 2002..Nevertheless, severe combined immunodeficiencies are a useful model, because gene transfer can confer a selective advantage to transduced cells. In this way, a proof of concept for gene therapy has been provided...
- Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapySalima Hacein-Bey-Abina
Laboratoire INSERM, , Paris, France
N Engl J Med 346:1185-93. 2002..CONCLUSIONS: Ex vivo gene therapy with gamma(c) can safely correct the immune deficiency of patients with X-linked severe combined immunodeficiency...
- [Gene therapy of children with X-linked severe combined immune deficiency: efficiency and complications]Alain Fischer
Inserm U.429, , 149, , 75015 Paris, France
Med Sci (Paris) 20:115-7. 2004
- Improving immune reconstitution while preventing graft-versus-host disease in allogeneic stem cell transplantationMarina Cavazzana-Calvo
, INSERM U429, , Paris, France
Semin Hematol 39:32-40. 2002....
- Is normal hematopoiesis maintained solely by long-term multipotent stem cells?Marina Cavazzana-Calvo
Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Paris, France
Blood 117:4420-4. 2011..The distribution of integration sites observed tends to support the validity of the revised model...
- Integration of retroviruses: a fine balance between efficiency and dangerAlain Fischer
Department and the Inserm Research Unit 429 at Necker University Hospital, Paris, France
PLoS Med 2:e10. 2005
- Gene therapy of inherited diseasesAlain Fischer
INSERM Unit 768, Paris, France. alain.fi
Lancet 371:2044-7. 2008
- [Cell therapy for inherited diseases of the hematopoietic system]Marina Cavazzana-Calvo
INSERM, U768, Paris and université René Descartes Paris 5, Hopital Necker Enfants Malades, 149, rue de Sevres, 75743 Paris Cedex 15, France
C R Biol 330:538-42. 2007..In this review, we have summarized the difficulties and the scientific advances leading us to improve the clinical results; the therapeutic research's track for primary immunodeficiencies is also discussed...
- Adenovirally transduced dendritic cells induce bispecific cytotoxic T lymphocyte responses against adenovirus and cytomegalovirus pp65 or against adenovirus and Epstein-Barr virus EBNA3C protein: a novel approach for immunotherapyYamina Hamel
INSERM U429, , 75743 Paris Cedex 15, France
Hum Gene Ther 13:855-66. 2002..Therefore, this approach could be considered in order to generate efficient virus cytolytic T cells to be used as adoptive immunotherapy in transplanted patients...
- Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafnessChantal Lagresle-Peyrou
Research Laboratory on Normal and Pathologic Development of the Immune System, U768, Institut National de la Sante et de la Recherche Medicale, 75015 Paris, France
Nat Genet 41:106-11. 2009..These results identify a previously unknown mechanism involved in regulation of hematopoietic cell differentiation and in one of the most severe human immunodeficiency syndromes...
- Evaluation of an algorithm based on peripheral blood hematopoietic progenitor cell and CD34+ cell concentrations to optimize peripheral blood progenitor cell collection by apheresisFrancois Lefrere
Département de Biothérapie, Service d Hématologie Adultes, and Laboratoire d Hématologie, Hopital Necker, 75743 Paris Cedex 15, France
Transfusion 47:1851-7. 2007..This prospective study has evaluated the potential of such method to predict the PBPC mobilization...
- Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patientsSophie Dupuis-Girod
Unité d Immunologie et d Hématologie Pédiatriques, Hopital Necker Enfants Malades, Paris, France
Pediatrics 111:e622-7. 2003..To evaluate the occurrence of autoimmune and inflammatory complications in Wiskott-Aldrich syndrome (WAS) and to determine risk factors and the prognosis of such complications with the aim of improving the definition of treatment options...
- Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiencyBenedicte Neven
Unité d Immuno Hématologie et Rhumatologie Pédiatrique, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris, Paris, France
Blood 113:4114-24. 2009..In most cases, HSCT enables long-term survival with infrequent sequelae. However, the occurrence of relatively late-onset complications is a concern that requires specific means of prevention and justifies careful patient follow-up...
- Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99Corinne Antoine
, , Paris, France
Lancet 361:553-60. 2003..For non-SCID, stem-cell transplantation can provide a cure, and grafts from unrelated donors are almost as beneficial as those from genetically HLA-identical relatives...
- The future of gene therapyMarina Cavazzana-Calvo
Immunology and Pediatric Haematology Unit, Hospital Necker, 75743 Paris, Cedex 15, France
Nature 427:779-81. 2004
- A hypomorphic R229Q Rag2 mouse mutant recapitulates human Omenn syndromeVeronica Marrella
Human Genome Department, Istituto di Tecnologie Biomediche, CNR, Via Fratelli Cervi 93, Segrate, Milan 20090, Italy
J Clin Invest 117:1260-9. 2007..In conclusion, Rag2(R229Q/R229Q) mice mimicked most symptoms of human OS; our findings support the notion that impaired immune tolerance and defective immune regulation are involved in the pathophysiology of OS...
- Gene therapy for severe combined immunodeficiency: are we there yet?Marina Cavazzana-Calvo
INSERM U768 and Université Paris Descartes, Paris, France
J Clin Invest 117:1456-65. 2007..In this review, we summarize the advantages and limitations associated with the use of gene therapy to cure SCID. Insertional mutagenesis and technological improvements aimed at increasing the safety of this strategy are also discussed...
- Transduced CD34+ cells from adrenoleukodystrophy patients with HIV-derived vector mediate long-term engraftment of NOD/SCID miceSonia Benhamida
INSERM U561, , 75014 Paris, France
Mol Ther 7:317-24. 2003..Transplantation of transduced ALD CD34(+) cells into NOD/SCID mice resulted in long-term expression of ALD protein in monocytes/macrophages derived from engrafted stem cells...
- Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006)Claire Booth
Molecular Immunology Unit, Institute of Child Health, University College London, and Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London WC1N 3JH, UK
Clin Immunol 123:139-47. 2007..Long-term follow-up of treated patients highlights a significant incidence of non-immunological problems with cognitive, neurological and audiological abnormalities most prominent...
- A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiencySalima Hacein-Bey-Abina
N Engl J Med 348:255-6. 2003
- [Curing a congenital immunologic deficiency]Nizar Mahlaoui
, , 75743 Paris 15
Rev Prat 57:1699-700. 2007
- Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patientsChantal Lagresle-Peyrou
Institut National de la Sante et de Recherche Medicale, Unit 768, Necker site, Paris, France
Mol Ther 16:396-403. 2008..This overall approach represents a useful tool for evaluating gene transfer efficiency in human SCID forms affecting B-cell development (such as Artemis deficiency) and for testing new vectors for improving in vivo RAG1 complementation...
- DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transferGary P Wang
University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
Nucleic Acids Res 36:e49. 2008..The methods described here should allow integration site populations from human gene therapy to be deeply characterized with spatial and temporal resolution...
- Gene therapy of X-linked severe combined immunodeficiencySalima Hacein-Bey-Abina
INSERM U 429, Gene and Cell Therapy Unit, Hĵpital Necker Enfants Malades, Paris, France
Int J Hematol 76:295-8. 2002..These 8 patients are doing well and living in a normal environment. This yet successful gene therapy demonstrates that in a setting where transgene expression provides a selective advantage, a clinical benefit can be expected...
- Gene therapy for human severe combined immunodeficienciesAlain Fischer
INSERM Unit 429, Gene Therapy Laboratory, Unit of Pediatric Immunology and Hematology, Necker Hospital, Paris, France
Isr Med Assoc J 4:51-4. 2002
- Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotypeMarina Cavazzana Calvo
Institut National de la Sante et de la Recherche Medicale, Unité 768, Paris, France
Blood 109:4575-81. 2007....
- CD34 stem cell top-ups without conditioning after initial haematopoietic stem cell transplantation for correction of incomplete haematopoietic and immunological recovery in severe congenital immunodeficienciesClaire Booth
Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UK
Br J Haematol 135:533-7. 2006..Unconditioned stem cell boosts have limited toxicity but should be given early after the original graft to be effective...
- Clonal evidence for the transduction of CD34+ cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trialManfred Schmidt
Department of Internal Medicine, University of Freiburg, Germany
Blood 105:2699-706. 2005..These results provide a first evidence in the setting of a clinical trial that CD34+ cells maintain both lymphomyeloid potential as well as self-renewal capacity after ex vivo manipulation...
- Gene therapy: X-SCID transgene leukaemogenicityAdrian J Thrasher
Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
Nature 443:E5-6; discussion E6-7. 2006..Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated...
- Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gammac cytokine receptor subunit or JAK-3 deficiencyCaroline Laffort
, , , Paris, France
Lancet 363:2051-4. 2004..That genetic causes are the only predisposing factor to be identified for severe combined immune deficiency, suggests that natural-killer cells or gammac/JAK-3-dependent signalling in keratinocytes could have a role in anti-HPV immunity...
- LMO2 and gene therapy for severe combined immunodeficiencyAlain Fischer
N Engl J Med 350:2526-7; author reply 2526-7. 2004
- Failure of SCID-X1 gene therapy in older patientsAdrian J Thrasher
Molecular Immunology Unit, Institute of Child Health, London, United Kingdom
Blood 105:4255-7. 2005..In particular, there is likely to be a limitation to initiation of normal thymopoiesis, and we therefore suggest that intervention for these patients should be considered as early as possible...
- Treatment of an infant with X-linked severe combined immunodeficiency (SCID-X1) by gene therapy in AustraliaSamantha L Ginn
Gene Therapy Research Unit, The Children's Hospital at Westmead and Children's Medical Research Unit, Sydney, NSW
Med J Aust 182:458-63. 2005....
- Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicityChantal Lagresle-Peyrou
Universite Paris Descartes, Faculte de Medecine, INSERM Unit 429, Site Necker Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex15, France
Blood 107:63-72. 2006....
- Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapyAnnette Deichmann
Institute for Molecular Medicine and Cell Research and Department of Internal Medicine I, German Cancer Research Center, University of Freiburg, Freiburg, Germany
J Clin Invest 117:2225-32. 2007..Beyond the observed cases of insertional mutagenesis in 3 patients, these data help to elucidate the relationship between vector insertion and long-term in vivo selection of transduced cells in human patients with SCID-X1...
- Bone marrow transplantation attenuates the myopathic phenotype of a muscular mouse model of spinal muscular atrophyNouzha Salah-Mohellibi
Molecular Neurogenetics Laboratory, , INSERM, U798, Evry, F-91057 France
Stem Cells 24:2723-32. 2006..Taken together, our data suggest that a biological activity is likely involved in muscle regeneration improvement mediated by BM transplantation. HGF may represent an attractive paracrine mechanism to support this activity...
- Gene therapy of metabolic diseasesAlain Fischer
INSERM, U768, Paris, France
J Inherit Metab Dis 29:409-12. 2006..A significant safety issue has also been observed. Several strategies are being experimentally tested for a number of metabolic diseases (more than 20) and may provide a rationale for the future development of clinical trials...
- Competition within the early B-cell compartment conditions B-cell reconstitution after hematopoietic stem cell transplantation in nonirradiated recipientsAllen Liu
, , Paris Cedex 15, France
Blood 108:1123-8. 2006....
- Human leucocyte antigen-identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft-versus-host disease and pre-existing viral infeRaffaele Renella
, , Paris, France
Br J Haematol 134:510-6. 2006..We suggest that the reduced survival after HLA-identical HSCT may be caused by the high incidence of pre-existing viral infections and associated with the onset of severe acute GVHD...
- Lymphoid-affiliated genes are associated with active histone modifications in human hematopoietic stem cellsJérôme Maës
Institut Universitaire d Hematologie, Universite Paris 7 Denis Diderot, Paris, France
Blood 112:2722-9. 2008..This permissive chromatin structure is progressively lost as the stem cell differentiates...
- Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IVDietke Buck
INSERM, , U429, , Paris, France
Eur J Immunol 36:224-35. 2006..These observations contrast with the severity of the clinical immunodeficiency, suggesting that Lig4 may have additional critical roles in lymphocyte survival beyond V(D)J recombination...
- HIV-1 Nef protein expression in human CD34+ progenitors impairs the differentiation of an early T/NK cell precursorCéline Dorival
INSERM U 841, Faculte de Medecine, Creteil, France
Virology 377:207-15. 2008..Altogether, these data demonstrate that Nef interferes with the differentiation of a primitive lymphoid human precursor with a T/NK potential...
- Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002Andrew R Gennery
Newcastle General Hospital, Westgate Rd, Newcastle upon Tyne, NE4 6BE United Kingdom
Blood 103:1152-7. 2004..Preexisting lung damage was the most important adverse risk factor. Further studies will determine optimal timing and type of HSCT...
- Allogeneic bone marrow transplantation in mevalonic aciduriaBenedicte Neven
Unité d Immuno Hématologie et Rhumatologie Pédiatrique, Assistance Publique Hopitaux de Paris, Paris, France
N Engl J Med 356:2700-3. 2007..We observed sustained remission of febrile attacks and inflammation during a 15-month follow-up period...
- A double-blind low dose-finding phase II study of granulocyte colony-stimulating factor combined with chemotherapy for stem cell mobilization in patients with non-Hodgkin's lymphomaFrancois Lefrere
Service d Hématologie Adultes, Centre d Investigation Clinique Hôpital Necker, Direction de la Recherche Clinique, AP HP, Paris, France
Haematologica 91:550-3. 2006..7%, 91%, 93.9 and 96.4%, respectively. Low G-CSF doses may be used with a similar probability of success as conventional doses and could allow significant savings...
- Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3Genevieve De Saint Basile
Unité Développement Normal et Pathologique du Système Immunitaire, INSERM U 429, Paris, France
J Clin Invest 114:1512-7. 2004..e., CD3epsilon deficiency, and emphasize the essential roles played by the CD3epsilon and CD3delta subunits in human thymocyte development, since these subunits associate with both the pre-TCR and the TCR...
- Dynamics of thymus-colonizing cells during human developmentRima Haddad
Laboratoire d'Immunologie Cellulaire et Immunopathologie de l'Ecole Pratique des Hautes Etudes and UMR 7151, Centre National de la Recherche Scientifique, , Paris, France
Immunity 24:217-30. 2006....
- Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow TransplantationHulya Ozsahin
Department of Pediatrics, Geneva University Hospital, Geneva, Switzerland
Blood 111:439-45. 2008....
- Bone marrow-derived mononuclear cell therapy induces distal angiogenesis after local injection in critical leg ischemiaJean Paul Duong Van Huyen
University Paris Descartes, Paris, France
Mod Pathol 21:837-46. 2008....