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3,176 results on '"Schmidt, Manfred"'

4. A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID

Author

Cesana, Daniela, Cicalese, Maria Pia, Calabria, Andrea, Merli, Pietro, Caruso, Roberta, Volpin, Monica, Rudilosso, Laura, Migliavacca, Maddalena, Barzaghi, Federica, Fossati, Claudia, Gazzo, Francesco, Pizzi, Simone, Ciolfi, Andrea, Bruselles, Alessandro, Tucci, Francesca, Spinozzi, Giulio, Pais, Giulia, Benedicenti, Fabrizio, Barcella, Matteo, Merelli, Ivan, Gallina, Pierangela, Giannelli, Stefania, Dionisio, Francesca, Scala, Serena, Casiraghi, Miriam, Strocchio, Luisa, Vinti, Luciana, Pacillo, Lucia, Draghi, Eleonora, Cesana, Marcella, Riccardo, Sara, Colantuono, Chiara, Six, Emmanuelle, Cavazzana, Marina, Carlucci, Filippo, Schmidt, Manfred, Cancrini, Caterina, Ciceri, Fabio, Vago, Luca, Cacchiarelli, Davide, Gentner, Bernhard, Naldini, Luigi, Tartaglia, Marco, Montini, Eugenio, Locatelli, Franco, and Aiuti, Alessandro

Published
2024
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5. Lovo‐cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB‐206 study

Author

Kanter, Julie, Thompson, Alexis A, Pierciey, Francis J, Hsieh, Matthew, Uchida, Naoya, Leboulch, Philippe, Schmidt, Manfred, Bonner, Melissa, Guo, Ruiting, Miller, Alex, Ribeil, Jean‐Antoine, Davidson, David, Asmal, Mohammed, Walters, Mark C, and Tisdale, John F

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Genetics, Clinical Trials and Supportive Activities, Sickle Cell Disease, Stem Cell Research, Hematology, Rare Diseases, Clinical Research, Gene Therapy, Humans, Lentivirus, Hematopoietic Stem Cell Transplantation, Anemia, Sickle Cell, Genetic Therapy, Hemoglobins, Cardiorespiratory Medicine and Haematology, Immunology, Cardiovascular medicine and haematology
Abstract

lovo-cel (bb1111; LentiGlobin for sickle cell disease [SCD]) gene therapy (GT) comprises autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified β-globin gene (βA-T87Q ) to produce anti-sickling hemoglobin (HbAT87Q ). The efficacy and safety of lovo-cel for SCD are being evaluated in the ongoing phase 1/2 HGB-206 study (ClinicalTrials.gov: NCT02140554). The treatment process evolved over time, using learnings from outcomes in the initial patients to optimize lovo-cel's benefit-risk profile. Following modest expression of HbAT87Q in the initial patients (Group A, n = 7), alterations were made to the treatment process for patients subsequently enrolled in Group B (n = 2, patients B1 and B2), including improvements to cell collection and lovo-cel manufacturing. After 6 months, median Group A peripheral blood vector copy number (≥0.08 c/dg) and HbAT87Q levels (≥0.46 g/dL) were inadequate for substantial clinical effect but stable and sustained over 5.5 years; both markedly improved in Group B (patient B1: ≥0.53 c/dg and ≥2.69 g/dL; patient B2: ≥2.14 c/dg and ≥6.40 g/dL, respectively) and generated improved biologic and clinical efficacy in Group B, including higher total hemoglobin and decreased hemolysis. The safety of the lovo-cel for SCD treatment regimen largely reflected the known side effects of HSPC collection, busulfan conditioning regimen, and underlying SCD; acute myeloid leukemia was observed in two patients in Group A and deemed unlikely related to insertional oncogenesis. Changes made during development of the lovo-cel treatment process were associated with improved outcomes and provide lessons for future SCD GT studies.

Published
2023

6. Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency

Author

Kohn, Donald B, Booth, Claire, Shaw, Kit L, Xu-Bayford, Jinhua, Garabedian, Elizabeth, Trevisan, Valentina, Carbonaro-Sarracino, Denise A, Soni, Kajal, Terrazas, Dayna, Snell, Katie, Ikeda, Alan, Leon-Rico, Diego, Moore, Theodore B, Buckland, Karen F, Shah, Ami J, Gilmour, Kimberly C, De Oliveira, Satiro, Rivat, Christine, Crooks, Gay M, Izotova, Natalia, Tse, John, Adams, Stuart, Shupien, Sally, Ricketts, Hilory, Davila, Alejandra, Uzowuru, Chilenwa, Icreverzi, Amalia, Barman, Provaboti, Campo Fernandez, Beatriz, Hollis, Roger P, Coronel, Maritess, Yu, Allen, Chun, Krista M, Casas, Christian E, Zhang, Ruixue, Arduini, Serena, Lynn, Frances, Kudari, Mahesh, Spezzi, Andrea, Zahn, Marco, Heimke, Rene, Labik, Ivan, Parrott, Roberta, Buckley, Rebecca H, Reeves, Lilith, Cornetta, Kenneth, Sokolic, Robert, Hershfield, Michael, Schmidt, Manfred, Candotti, Fabio, Malech, Harry L, Thrasher, Adrian J, and Gaspar, H Bobby

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Biotechnology, Transplantation, Gene Therapy, Genetics, Regenerative Medicine, Clinical Research, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Evaluation of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, Good Health and Well Being, Adenosine Deaminase, Adolescent, Agammaglobulinemia, Child, Child, Preschool, Genetic Therapy, Genetic Vectors, Hematopoietic Stem Cell Transplantation, Humans, Infant, Lentivirus, Lymphocyte Count, Progression-Free Survival, Prospective Studies, Severe Combined Immunodeficiency, Transplantation, Autologous, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundSevere combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency.MethodsWe treated 50 patients with ADA-SCID (30 in the United States and 20 in the United Kingdom) with an investigational gene therapy composed of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human ADA. Data from the two U.S. studies (in which fresh and cryopreserved formulations were used) at 24 months of follow-up were analyzed alongside data from the U.K. study (in which a fresh formulation was used) at 36 months of follow-up.ResultsOverall survival was 100% in all studies up to 24 and 36 months. Event-free survival (in the absence of reinitiation of enzyme-replacement therapy or rescue allogeneic hematopoietic stem-cell transplantation) was 97% (U.S. studies) and 100% (U.K. study) at 12 months; 97% and 95%, respectively, at 24 months; and 95% (U.K. study) at 36 months. Engraftment of genetically modified HSPCs persisted in 29 of 30 patients in the U.S. studies and in 19 of 20 patients in the U.K. study. Patients had sustained metabolic detoxification and normalization of ADA activity levels. Immune reconstitution was robust, with 90% of the patients in the U.S. studies and 100% of those in the U.K. study discontinuing immunoglobulin-replacement therapy by 24 months and 36 months, respectively. No evidence of monoclonal expansion, leukoproliferative complications, or emergence of replication-competent lentivirus was noted, and no events of autoimmunity or graft-versus-host disease occurred. Most adverse events were of low grade.ConclusionsTreatment of ADA-SCID with ex vivo lentiviral HSPC gene therapy resulted in high overall and event-free survival with sustained ADA expression, metabolic correction, and functional immune reconstitution. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01852071, NCT02999984, and NCT01380990.).

Published
2021

7. HIV- 1 lentivirus tethering to the genome is associated with transcription factor binding sites found in genes that favour virus survival

Author

Suleman, Saqlain, Payne, Annette, Bowden, Johnathan, Haque, Sharmin Al, Zahn, Marco, Fawaz, Serena, Khalifa, Mohammad S., Jobling, Susan, Hay, David, Franco, Matteo, Fronza, Raffaele, Wang, Wei, Strobel-Freidekind, Olga, Deichmann, Annette, Takeuchi, Yasuhiro, Waddington, Simon N., Gil-Farina, Irene, Schmidt, Manfred, and Themis, Michael

Published
2022
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9. Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease

Author

Hsieh, Matthew M, Bonner, Melissa, Pierciey, Francis John, Uchida, Naoya, Rottman, James, Demopoulos, Laura, Schmidt, Manfred, Kanter, Julie, Walters, Mark C, Thompson, Alexis A, Asmal, Mohammed, and Tisdale, John F

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Rare Diseases, Orphan Drug, Sickle Cell Disease, Hematology, Genetics, Stem Cell Research, Gene Therapy, Biotechnology, Blood, Anemia, Sickle Cell, Genetic Therapy, Humans, Lentivirus, Myelodysplastic Syndromes, Cardiovascular medicine and haematology
Abstract

Ability to accurately attribute adverse events post–gene therapy is required to describe the benefit-risk of these novel treatments. A SCD patient developed myelodysplastic syndrome post-LentiGlobin treatment; we show how insertional oncogenesis was excluded as the cause.

Published
2020

14. Long-term outcomes of lentiviral gene therapy for the β-hemoglobinopathies: the HGB-205 trial

Author

Magrin, Elisa, Semeraro, Michaela, Hebert, Nicolas, Joseph, Laure, Magnani, Alessandra, Chalumeau, Anne, Gabrion, Aurélie, Roudaut, Cécile, Marouene, Jouda, Lefrere, Francois, Diana, Jean-Sebastien, Denis, Adeline, Neven, Bénédicte, Funck-Brentano, Isabelle, Negre, Olivier, Renolleau, Sylvain, Brousse, Valentine, Kiger, Laurent, Touzot, Fabien, Poirot, Catherine, Bourget, Philippe, El Nemer, Wassim, Blanche, Stéphane, Tréluyer, Jean-Marc, Asmal, Mohammed, Walls, Courtney, Beuzard, Yves, Schmidt, Manfred, Hacein-Bey-Abina, Salima, Asnafi, Vahid, Guichard, Isabelle, Poirée, Maryline, Monpoux, Fabrice, Touraine, Philippe, Brouzes, Chantal, de Montalembert, Mariane, Payen, Emmanuel, Six, Emmanuelle, Ribeil, Jean-Antoine, Miccio, Annarita, Bartolucci, Pablo, Leboulch, Philippe, and Cavazzana, Marina

Published
2022
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15. Sozialpolitik

Author

Schmidt, Manfred G., Andersen, Uwe, editor, Bogumil, Jörg, editor, Marschall, Stefan, editor, and Woyke, Wichard, editor

Published
2021
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