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Reconstitution immunitaire et immunothérapie adoptive anti-virales après allogreffe de cellules souches hématopoiétiques

Abstract : Hematopoietic stem cells Transplantation (HSCT) is a well recognized strategy for treatment of haematological malignancies. However, HSCT complications among which the viral infections a reassociated with high morbidity and mortality. These infections arise in the absence of immune reconstitution. Monitoring of viral reactivations after allogeneic HSCT is necessary, to identify patients at risk of viral infections, but not sufficient, as patients may be abusively treated. In this work we propose to combine viral DNA load assessment with specific immune monitoring to target patients who need to be treated. We report a retrospective study investigating EBV infection and EBV-specific immune recovery using the functional IFN Elispot assay in 40 allogeneic HSCT patients. We initiated a similar study with ADV which is pending. However, although patients are correctly targeted, anti-viral treatment is sometimes not effective. We present a study on the development of a complete clinical grade generation of Human anti-Adenovirus cytotoxic T cells in GMP (Good Manufacturing Practice) conditions, thanks to the system CliniMACS and the Cytokine Capture System, to propose an adoptive immunotherapy to the recipient.We describe afterwards three clinical experiments of treatment of an ADV infection after HSCT.Finally, we present the preliminary results of the anti-ADV and -CMV bi-specific CTL production.
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Lamia Rothé. Reconstitution immunitaire et immunothérapie adoptive anti-virales après allogreffe de cellules souches hématopoiétiques. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2010. Français. ⟨NNT : 2010NAN10073⟩. ⟨tel-01748654⟩

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