期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 31, 页码 13824-13829出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1008051107
关键词
cancer vaccine; active specific immunotherapy; phase I clinical trial
资金
- Argos Therapeutics [US7547551]
- Antwerp University Hospital from the European Hematology Association (EHA)
- Belgian Foundation Against Cancer [SCIE216-2008]
- University of Antwerp
- Fund for Scientific Research Flanders (FWO-Vlaanderen) [G.0082.08]
- Agency for Innovation by Technology and Science (IWT-TBM) [80664]
- National Cancer Plan (Action 29) of the Belgian government
- Stichting Emmanuel van der Schueren of the Vlaamse Liga tegen Kanker
- MRC [G0501963] Funding Source: UKRI
- Medical Research Council [G0501963] Funding Source: researchfish
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.
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