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RESEARCH PRODUCT

Towards More Specificity and Effectivity in the Antileukemia Immune Response

subject

description

Experimental and clinical studies have shown that alloreactive T-cell responses derived from donor lymphocytes can effectively eliminate leukemia cells after allogeneic hematopoietic stem cell transplantation. However, there are still too many patients in whom this graft-versus-leukemia reactivity is insufficient to prevent leukemia relapse or who suffer from severe alloreactivity to nonmalignant host tissues also mediated by donor-derived T cells. Therefore, various conceptually different approaches have been developed at the level of donor T cells in order to improve the efficacy of leukemia-directed immunity while reducing the incidence of unwanted graft-versus-host disease. As outlined in this chapter, these approaches include myeloid leukemia vaccines to specifically stimulate leukemia-reactive T cells as well as the selective depletion of alloreactive T cells or even entire T-cell subsets and the add-back of undepleted cell fractions after transplantation. Early experimental and clinical results have demonstrated the safety of these approaches and remarkable efficacy in single patients. Moving them now forward will require randomized prospective clinical trials to define the precise role of these immunotherapeutic agents preferably in prophylactic and preemptive disease settings.