Academic Journal
Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy
| العنوان: | Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy |
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| المؤلفون: | Portevin, Damien, Poupot, Mary, Rolland, Olivier, Turrin, Cédric-Olivier, Fournié, Jean-Jacques, Majoral, Jean Pierre, Caminade, Anne-Marie, Poupot, Rémy |
| المساهمون: | Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), D. P. was the recipient of a Fellowship from the Association pour la Recherche contre le Cancer (ARC). This work was supported by the Institut National de la Sante et de la Recherche Medicale (INSERM, France), Paul Sabatier University and the Institut National du Cancer (INCa) and the Region Midi-Pyrenees. |
| المصدر: | EISSN: 1479-5876 ; Journal of Translational Medicine ; https://inserm.hal.science/inserm-00668486 ; Journal of Translational Medicine, 2009, 7 (1), pp.82. ⟨10.1186/1479-5876-7-82⟩ |
| بيانات النشر: | HAL CCSD BioMed Central |
| سنة النشر: | 2009 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | MESH: Adult, MESH: Animals, MESH: Diphosphonates, MESH: Humans, MESH: Immunotherapy, Adoptive, MESH: Interleukin-2, MESH: Killer Cells, Natural, MESH: Leukocytes, Mononuclear, MESH: Lymphocyte Activation, MESH: Molecular Structure, MESH: CD4-Positive T-Lymphocytes, MESH: Cell Proliferation, MESH: Cells, Cultured, MESH: Dendrimers, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology |
| الوصف: | International audience ; BACKGROUND: Adoptive cell therapy with allogenic NK cells constitutes a promising approach for the treatment of certain malignancies. Such strategies are currently limited by the requirement of an efficient protocol for NK cell expansion. We have developed a method using synthetic nanosized phosphonate-capped dendrimers allowing such expansion. We are showing here that this is due to a specific inhibitory activity towards CD4+ T cell which could lead to further medical applications of this dendrimer. METHODS: Mononuclear cells from human peripheral blood were used to investigate the immunomodulatory effects of nanosized phosphonate-capped dendrimers on interleukin-2 driven CD4+T cell expansion. Proliferation status was investigated using flow cytometry analysis of CFSE dilution and PI incorporation experiments. Magnetic bead cell sorting was used to address activity towards individual or mixed cell sub-populations. We performed equilibrium binding assay to assess the interaction of fluorescent dendrimers with pure CD4+ T cells. RESULTS: Phosphonate-capped dendrimers are inhibiting the activation, and therefore the proliferation; of CD4+ T cells in IL-2 stimulated PBMCs, without affecting their viability. This allows a rapid enrichment of NK cells and further expansion. We found that dendrimer acts directly on T cells, as their regulatory property is maintained when stimulating purified CD4+ T cells with anti-CD3/CD28 microbeads. Performing equilibrium binding assays using a fluorescent analogue, we show that the phosphonate capped-dendrimers are specifically interacting with purified CD4+ T cells. Ultimately, we found that our protocol prevents the IL-2 related expansion of regulatory T cells that would be deleterious for the activity of infused NK cells. CONCLUSION: High yield expansion of NK cells from human PBMCs by phosphonate-capped dendrimers and IL-2 occurs through the specific inhibition of the CD4+ lymphocyte compartment. Given the specificity of the interaction of dendrimers ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/19778420; inserm-00668486; https://inserm.hal.science/inserm-00668486; https://inserm.hal.science/inserm-00668486/document; https://inserm.hal.science/inserm-00668486/file/1479-5876-7-82.pdf; PUBMED: 19778420 |
| DOI: | 10.1186/1479-5876-7-82 |
| الاتاحة: | https://inserm.hal.science/inserm-00668486 https://inserm.hal.science/inserm-00668486/document https://inserm.hal.science/inserm-00668486/file/1479-5876-7-82.pdf https://doi.org/10.1186/1479-5876-7-82 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.F7967DDB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/1479-5876-7-82 |
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