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oai:recercat.cat:11351/62782024-12-13T09:47:47Zcom_2072_378071com_2072_378040col_2072_378097

2023-11-08T15:27:03Z urn:hdl:11351/6278 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 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). 2023-11-08T15:27:03Z 2023-11-08T15:27:03Z 2021-09-08T07:38:53Z 2021-09-08T07:38:53Z 2020-02-25 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/6278 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 Frontiers Media Scientia