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The main complications of allogeneic hematopoietic stem cell transplantation (HSCT) include graft-versus-host disease (GVHD) and poor immune reconstitution leading to severe infections and leukemia relapse. Mature donor T-cells present in the transplant facilitate T-cell reconstitution but also induce GVHD, which itself impairs immune reconstitution. We have developed a strategy of alloreactive T-cell depletion, using T-cells expressing the Herpes simplex thymidine kinase (TK) suicide gene combined with a ganciclovir (GCV) treatment. This system permits the selective elimination of dividing TK+ T-cells in vivo. To test this hypothesis in preclinical settings, we have previously developed several experimental models of GVHD using TK+ T-cells in mice. The demonstration that a preventive treatment with GCV administered close to the time of HSCT could control GVHD brought the proof of concept. We now propose a clinical trial to test whether donor lymphocytes infusion (DLI) using TK-transduced cells permits to induce a graft-versus-tumor (GVT) effect for treatment of relapse after HSCT, while GVHD can be controlled by GCV treatment.
DLI-TK is administered either after failure of 1 or several previous standard (std-) DLI of, defined after a minimal follow-up of 2 months after the last injection. To prepare DLI-TK, donor T-cells are transduced with a retroviral vector encoding TK. Transduced cells are selected using a CliniMACS device (MYLTENYI). In case of previous std-DLI received, the DLI-TK cell dose is adjusted to be below or equal to the maximal cell dose previously received in std-DLI. No comparison is planned in the analysis.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
donor lymphocyte infusion
Groupe Hospitalier Albert Chenevier-Henri Mondor
Assistance Publique - Hôpitaux de Paris
Published on BioPortfolio: 2014-08-27T03:15:12-0400
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The transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
Transfer of GASTROINTESTINAL MICROBIOTA from one individual to another by infusion of donor FECES to the upper or lower GASTROINTESTINAL TRACT of the recipient.
Endogenous superantigens responsible for inducing strong proliferative responses in T-cells in mixed lymphocyte reactions (see LYMPHOCYTE CULTURE TEST, MIXED). They are encoded by mouse mammary tumor viruses that have integrated into the germ line as DNA proviruses (MINOR LYMPHOCYTE STIMULATORY LOCI).
Use of any infusion therapy on an ambulatory, outpatient, or other non-institutionalized basis.
Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...