ArticleJournal of translational medicine2015
Generation of lentivirus-induced dendritic cells under GMP-compliant conditions for adaptive immune reconstitution against cytomegalovirus after stem cell transplantation.
Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Potency assays and biomarkers for cell-based advanced therapy medicinal products.Frontiers in immunology · 2023Review
- Induced dendritic cells co-expressing GM-CSF/IFN-α/tWT1 priming T and B cells and automated manufacturing to boost GvL.Molecular therapy. Methods & clinical development · 2021Article
- Recent Advances in Good Manufacturing Practice-Grade Generation of Dendritic Cells.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2020Review
- Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV.PLoS pathogens · 2020Article
- Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications.Frontiers in immunology · 2020Review
- Monocytes reprogrammed with lentiviral vectors co-expressing GM-CSF, IFN-α2 and antigens for personalized immune therapy of acute leukemia pre- or post-stem cell transplantation.Cancer immunology, immunotherapy : CII · 2019Review
- Manufacture of Third-Generation Lentivirus for Preclinical Use, with Process Development Considerations for Translation to Good Manufacturing Practice.Human gene therapy methods · 2018Article
- Reconstructing the immune system with lentiviral vectors.Virus genes · 2017Review
- Targeting of the WT1Cancer immunology, immunotherapy : CII · 2017Article
- Multidimensional Analysis Integrating Human T-Cell Signatures in Lymphatic Tissues with Sex of Humanized Mice for Prediction of Responses after Dendritic Cell Immunization.Frontiers in immunology · 2017Article
- Recent Advances in Lentiviral Vaccines for HIV-1 Infection.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReactivation of latent viruses such as human cytomegalovirus (HCMV) after allogeneic hematopoietic stem cell transplantation (HSCT) results in high morbidity and mortality. Effective immunization against HCMV shortly after allo-HSCT is an unmet clinical need due to delayed adaptive T cell development. Donor-derived dendritic cells (DCs) have a critical participation in stimulation of naïve T cells and immune reconstitution, and therefore adoptive DC therapy could be used to protect patients after HSCT. However, previous methods for ex vivo generation of adoptive donor-derived DCs were complex and inconsistent, particularly regarding cell viability and potency after thawing. We have previously demonstrated in humanized mouse models of HSCT the proof-of-concept of a novel modality of lentivirus-induced DCs ("SmyleDCpp65") that accelerated antigen-specific T cell development.
methodsHere we demonstrate the feasibility of good manufacturing practices (GMP) for production of donor-derived DCs consisting of monocytes from peripheral blood transduced with an integrase-defective lentiviral vector (IDLV, co-expressing GM-CSF, IFN-α and the cytomegalovirus antigen pp65) that were cryopreserved and thawed.
resultsUpscaling and standardized production of one lot of IDLV and three lots of SmyleDCpp65 under GMP-compliant conditions were feasible. Analytical parameters for quality control of SmyleDCpp65 identity after thawing and potency after culture were defined. Cell recovery, uniformity, efficacy of gene transfer, purity and viability were high and consistent. SmyleDCpp65 showed only residual and polyclonal IDLV integration, unbiased to proto-oncogenic hot-spots. Stimulation of autologous T cells by GMP-grade SmyleDCpp65 was validated.
conclusionThese results underscore further developments of this individualized donor-derived cell vaccine to accelerate immune reconstitution against HCMV after HSCT in clinical trials.
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