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

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-gamma-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.

• Authors: Viggo F Van Tendeloo, Ann Van de Velde, Ann Van Driessche, Nathalie Cools, Sébastien Anguille, Kristin Ladell, Emma Gostick, Katrien Vermeulen, Katrien Pieters, Griet Nijs, Barbara Stein, Evelien L Smits, Wilfried A Schroyens, Alain P Gadisseur, Inge Vrelust, Philippe G Jorens, Herman Goossens, I Jolanda de Vries, David A Price, Yusuke Oji, Yoshihiro Oka, Haruo Sugiyama, Zwi N Berneman
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 31 Pg. 13824-9 (Aug 03 2010) ISSN: 1091-6490 [Electronic] United States
• PMID: 20631300 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• RNA, Messenger
• WT1 Proteins
• Interferon-gamma

Topics

• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cancer Vaccines (immunology)
• Dendritic Cells (immunology)
• Humans
• Interferon-gamma (biosynthesis, immunology)
• Leukemia, Myeloid, Acute (immunology, therapy)
• RNA, Messenger (genetics)
• Remission Induction
• Vaccination
• WT1 Proteins (genetics, immunology)