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Characterization of a Cytomegalovirus-Specific T Lymphocyte Product Obtained Through a Rapid and Scalable Production Process for Use in Adoptive Immunotherapy Grau Vorster, Marta Lopez Montañes, Maria Canto Puig, Ester Vives Armengol, Joaquim Oliver-Vila, Irene Barba Suñol, Pere Rudilla Salvador, Francesc Institut Català de la Salut [Grau-Vorster M, López-Montañés M, Cantó E, Rudilla F] Cell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain. Grup de Medicina Transfusional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Vives J] Cell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain. Grup de Medicina Transfusional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Grup d’Enginyeria tissular musculoesquelètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Oliver-Vila I] Cell Therapy Service, Banc de Sang i Teixits, Barcelona, Spain. [Barba P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain Vall d'Hebron Barcelona Hospital Campus Infeccions per citomegalovirus Cèl·lules T Immunoteràpia ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Cytokine-Induced Killer Cells::T-Lymphocytes, Cytotoxic DISEASES::Virus Diseases::DNA Virus Infections::Herpesviridae Infections::Cytomegalovirus Infections ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Herpesviridae::infecciones por Citomegalovirus TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::células asesinas inducidas por citocinas::linfocitos T citotóxicos Immunoteràpia adoptiva; Citotoxicitat; Limfòcits T específics del virus (VST) Inmunoterapia adoptiva; Citotoxicidad; Linfocitos T específicos de virus (VST) Adoptive immunotherapy; Cytotoxicity; Virus specific T lymphocytes (VST) Immunosuppressed patients are susceptible to virus reactivation or de novo infection. Adoptive immunotherapy, based on virus-specific T lymphocytes (VST), can prevent or treat viral diseases. However, donor availability, HLA-compatibility restrictions, high costs, and time required for the production of personalized medicines constitute considerable limitations to this treatment. Ex vivo rapid and large-scale expansion of VST, compliant with current good manufacturing practice (cGMP) standards, with an associated cell donor registry would overcome these limitations. This study aimed to characterize a VST product obtained through an expansion protocol transferable to cGMP standards. Antigenic stimulus consisted of cytomegalovirus (CMV) pp65 peptide pool-pulsed autologous dendritic cells (DCs) derived from monocytes. G-Rex technology, cytokines IL-2, IL-7, and IL-15, and anti-CD3 and anti-CD28 antibodies were used for culture. At day 14 of cell culture, the final product was characterized regarding T cell subsets, specificity, and functionality. The final product, comprised mainly CD4+ and CD8+ T lymphocytes (49.2 ± 24.7 and 42.3 ± 25.2, respectively). The culture conditions made it possible to achieve at least a 98.89-fold increase in pp65-specific CD3+ IFN-γ+ cells. These cells were specific, as pp65-specific cytotoxicity was demonstrated. Additionally, in complete HLA mismatch and without the presence of pp65, alloreactivity resulted in <5% cell lysis. In conclusion, a cGMP scalable process for the generation of a large number of doses of CMV-specific cytotoxic T cells was successfully performed. Work in our laboratory was supported by the Spanish Cell Therapy Network (TerCel, file No. RD16/0011/0028), and carried out as part of AdvanceCat with the support of ACCIÓ (Catalonia Trade & Investment; Catalan government) under the Catalonian ERDF operational program (European Regional Development Fund) 2014-2020. Our laboratory was certified by the Catalan government as a Consolidated Research Group (ref. 2017SGR719). 2021-09-08T07:38:53Z 2021-09-08T07:38:53Z 2020-02-25 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Grau-Vorster M, López-Montañés M, Cantó E, Vives J, Oliver-Vila I, Barba P, et al. Characterization of a Cytomegalovirus-Specific T Lymphocyte Product Obtained Through a Rapid and Scalable Production Process for Use in Adoptive Immunotherapy. Front Immunol. 2020 Feb 25;11:271. 1664-3224 https://hdl.handle.net/11351/6278 10.3389/fimmu.2020.00271 32161589 000524779300001 http://hdl.handle.net/11351/6278 eng Frontiers in Immunology;11 https://doi.org/10.3389/fimmu.2020.00271 info:eu-repo/grantAgreement/ES/PE2013-2016/RD16%2F0011%2F0028 info:eu-repo/grantAgreement/ES/PERIS2016-2020/2017SGR719 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf Frontiers Media Scientia