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161 Dendritic Cell Vaccination in Acute Myeloid Leukemia

Berneman, Zwi N; Velde, Ann Van de; Anguille, Sébastien; Cools, Nathalie; Van Driessche, Ann; Van Tendeloo, Viggo F

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 67
doi: 10.1097/01.qai.0000397347.92555.5c

University of Antwerp and Antwerp University Hospital, Edegem, Belgium

Active immunization using tumor antigen-loaded dendritic cells (DC) holds promise for the adjuvant treatment of cancer to control residual disease, but so far most DC trials have been performed in end-stage cancer patients with high tumor load. Here, in a phase I/II trial, we investigated the effect of autologous DC vaccination in 17 patients with acute myeloid leukemia (AML) in remission but at high risk of full relapse. The Wilms' tumor 1 protein (WT1), a nearly universal tumor antigen, was chosen as an immunotherapeutic target because of its established role in leukemogenesis and superior immunogenic characteristics. Two out of 3 patients who were in partial remission with morphologically demonstrable disease after chemotherapy were brought into complete remission following intradermal administration of WT1 mRNA-electroporated DC. In those 2 patients as well as in 7 other patients who were in complete remission but who had molecularly demonstrable residual disease, there was a return to normal of the AML-associated tumor marker following DC vaccination, compatible with the induction of molecular remission in 9/17 patients vaccinated thus far. Survival in responders is significantly longer than in non-responders. Immunomonitoring showed a significant increase in WT1-specific CD8+ T cells and signs of general immune stimulation, such as a significant increase of plasma levels of interleukin 2 and of HLA-DR+ CD4+ T-cells. Clinical responses were correlated with elevated levels of activated natural killer cells post-vaccination, but long-term responses were only correlated with an increase in WT1-specific CD8+ T-cell frequencies. There was no significant change post-vaccination in WT1 antibody levels. In conclusion, vaccination with WT1 mRNA-loaded DC elicits immunological and clinical responses in AML patients. DC-based immunotherapy emerges as a feasible and effective strategy to control residual disease and prevent full relapse in AML. Reference: Van Tendeloo VF et al. Proc Natl Acad Sci USA 2010;107:13824-13829.

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