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Project

Recipient-mediated antileukemic effects after allogeneic hematopoietic stem cell transplantation: studies in mice.

Allogeneic hematopoietic stem cell transplantation is a cornerstone in the treatment of several hematological malignancies such as leukemias. Is is well known that the donor immune system (that engrafts after transplantation) can destroy residual tumor cells, and this so-called graft-versus-leukemia effect critically determines the curative potential of the procedure. Donor T cells play a critical role and this is exploited in posttransplant immunotherapeutic strategies such as donor lymphocyte infusion. However, donor T cells also cause graft-versus-host-disease, an important cause of morbidity and mortality. In this research project 2 novel experimental strategies are explored in which the recipient immune system is stimulated to mediate antileukemic effects. Theoretically, this strategy does not hold a risk for graft-versus-host disease. To this end, mouse models of allogeneic bone marrow transplantation are used to examine 1° post transplant therapy with blocking anti-CTLA-4 antibodies, and 2° posttransplant treatment with recipient-type lymphocytes (instead of donor-type lymphocytes in donor lymphocyte infusion). This projects aims to unravel the effector mechanisms of the antileukemic effect seen with these new strategies in mice, and characterize associated complications, such as autoimmunity after CTLA-4-blockade.
Date:1 Jan 2010 →  31 Dec 2013
Keywords:graft-versus-leukemia, allogeneic hematopoietic stem cell trans, Transplantation immunology
Disciplines:Immunology