35 research outputs found

    Lentiviral gene therapy for X-linked chronic granulomatous disease

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    Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4–1.8 copies per neutrophil) and the persistence of 16–46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients

    Dendritic cells and parasites: from recognition and activation to immune response instruction

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    The effective defense against parasite infections requires the ability to mount an appropriate and controlled specific immune response able to eradicate the invading pathogen while limiting the collateral damage to self-tissues. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. Ligation of dendritic cell pattern recognition receptors by pathogen-associated molecular pattern present in the parasites initiates signaling pathways that lead to the production of surface and secreted proteins that are required, together with the antigen, to induce an appropriate and timely regulated immune response. There is evidence showing that parasites can influence and regulate dendritic cell functions in order to promote a more permissive environment for their survival. In this review, we will focus on new insights about the ability of protozoan and helminth parasites or their products to modify dendritic cell function and discuss how this interaction is crucial in shaping the host response.Fil: Motran, Claudia Cristina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂ­mica ClĂ­nica e InmunologĂ­a; ArgentinaFil: Ambrosio, Laura Fernanda. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂ­mica ClĂ­nica e InmunologĂ­a; ArgentinaFil: Volpini, Ximena. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂ­mica ClĂ­nica e InmunologĂ­a; ArgentinaFil: Celias, Daiana Pamela. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂ­mica ClĂ­nica e InmunologĂ­a; ArgentinaFil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂ­mica ClĂ­nica e InmunologĂ­a; Argentin
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