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.
journal_name
Proc Natl Acad Sci U S Aauthors
Van Tendeloo VF,Van de Velde A,Van Driessche A,Cools N,Anguille S,Ladell K,Gostick E,Vermeulen K,Pieters K,Nijs G,Stein B,Smits EL,Schroyens WA,Gadisseur AP,Vrelust I,Jorens PG,Goossens H,de Vries IJ,Price DA,Oji Ydoi
10.1073/pnas.1008051107subject
Has Abstractpub_date
2010-08-03 00:00:00pages
13824-9issue
31eissn
0027-8424issn
1091-6490pii
1008051107journal_volume
107pub_type
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