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Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination

Van Tendeloo, V. F., Van de Velde, A., Van Driessche, A., Cools, N., Anguille, S., Ladell, Kristin Ingrid, Gostick, Emma, Vermeulen, K., Pieters, K., Nijs, G., Stein, B., Smits, E. L., Schroyens, W. A., Gadisseur, A. P., Vrelust, I., Jorens, P. G., Goossens, H., de Vries, I. J., Price, David A., Oji, Y., Oka, Y., Sugiyama, H. and Berneman, Z. N. 2010. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proceedings of the National Academy of Sciences of the United States of America 107 (31) , pp. 13824-13829. 10.1073/pnas.1008051107

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Abstract

Active immunization using tumor antigen-loaded dendritic cells holds promise for the adjuvant treatment of cancer to eradicate or control residual disease, but so far, most dendritic cell trials have been performed in end-stage cancer patients with high tumor loads. Here, in a phase I/II trial, we investigated the effect of autologous dendritic cell vaccination in 10 patients with acute myeloid leukemia (AML). 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 patients in partial remission after chemotherapy were brought into complete remission after intradermal administration of full-length WT1 mRNA-electroporated dendritic cells. In these two patients and three other patients who were in complete remission, the AML-associated tumor marker returned to normal after dendritic cell vaccination, compatible with the induction of molecular remission. Clinical responses were correlated with vaccine-associated increases in WT1-specific CD8+ T cell frequencies, as detected by peptide/HLA-A*0201 tetramer staining, and elevated levels of activated natural killer cells postvaccination. Furthermore, vaccinated patients showed increased levels of WT1-specific IFN-γ–producing CD8+ T cells and features of general immune activation. These data support the further development of vaccination with WT1 mRNA-loaded dendritic cells as a postremission treatment to prevent full relapse in AML patients.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: cancer vaccine; active specific immunotherapy; phase 1 clinical trial
Publisher: National Academy of Sciences
ISSN: 0027-8424
Last Modified: 07 Mar 2019 22:06
URI: http://orca.cf.ac.uk/id/eprint/25205

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