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Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

التفاصيل البيبلوغرافية
العنوان: Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial
المؤلفون: Yingying Wang, Chongsheng Qian, Bénédicte Bruno, Isabelle Clerc Urmes, Huili Cai, Patrice Ceballos, Cécile Pochon, Jean Hugues Dalle, Arnaud Campidelli, Marcelo De Carvalho Bittencourt, Nadine Petitpain, Danièle Bensoussan, Maud D'Aveni, Catherine Paillard, Hélène Jeulin, Loïc Reppel, Charlotte Jubert, Clément Cholle, Aude Marie-Cardine, Véronique Decot, Stephane Vigouroux, Claire Galambrun, Véronique Venard, Alexandra Salmon, Laurence Clement
المساهمون: Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Unité de Thérapie Cellulaire et Tissulaire [CHU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie [CHRU Nancy], Service de Virologie [CHRU Nancy], Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Hôpital Jeanne de Flandre [Lille], Hôpital de Hautepierre [Strasbourg], Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Charles Nicolle [Rouen], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Faculté de Pharmacie [Nancy], Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine)
المصدر: Journal of Hematology and Oncology
Journal of Hematology and Oncology, BioMed Central, 2017, 10 (1), ⟨10.1186/s13045-017-0469-0⟩
Journal of Hematology & Oncology
Journal of Hematology & Oncology, CAHON, 2017, 10 (1), ⟨10.1186/s13045-017-0469-0⟩
Journal of Hematology & Oncology, Vol 10, Iss 1, Pp 1-14 (2017)
بيانات النشر: Springer Science and Business Media LLC, 2017.
سنة النشر: 2017
مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, Cancer Research, [SDV]Life Sciences [q-bio], viruses, medicine.medical_treatment, Graft vs Host Disease, T-Cell Antigen Receptor Specificity, Hematopoietic stem cell transplantation, Immunotherapy, Adoptive, Adenovirus Infections, Human, 0302 clinical medicine, T-Lymphocyte Subsets, Child, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Hematology, Viral Load, Allografts, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Tissue Donors, 3. Good health, Treatment Outcome, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Interferon-γ-based immunomagnetic isolation, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cord Blood Stem Cell Transplantation, Viral load, Immunosuppressive Agents, Adult, Third party haploidentical donor, medicine.medical_specialty, Adolescent, T cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, lcsh:RC254-282, Interferon-gamma, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Leukapheresis, Viremia, Adenovirus infection, Molecular Biology, Umbilical cord blood transplantation, Immunomagnetic Separation, lcsh:RC633-647.5, business.industry, Umbilical Cord Blood Transplantation, Research, Adenoviruses, Human, medicine.disease, Allogeneic stem cell transplantation, Transplantation, 030104 developmental biology, Graft-versus-host disease, Transplantation, Haploidentical, Immunology, Virus Activation, Adenovirus-specific T cells, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
الوصف: Background Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered). Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0469-0) contains supplementary material, which is available to authorized users.
تدمد: 1756-8722
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce101a3809a77b9511c0fc557412ab28
https://doi.org/10.1186/s13045-017-0469-0
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....ce101a3809a77b9511c0fc557412ab28
قاعدة البيانات: OpenAIRE
الوصف
تدمد:17568722