Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination.
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.
Van Tendeloo
Viggo F
VF
University of Antwerp, Faculty of Medicine, Vaccine and Infectious Disease Institute (Vaxinfectio) and Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp B-2650, Belgium. Viggo.Van.Tendeloo@uza.be
Van de Velde
Ann
A
Van Driessche
Ann
A
Cools
Nathalie
N
Anguille
Sébastien
S
Ladell
Kristin
K
Gostick
Emma
E
Vermeulen
Katrien
K
Pieters
Katrien
K
Nijs
Griet
G
Stein
Barbara
B
Smits
Evelien L
EL
Schroyens
Wilfried A
WA
Gadisseur
Alain P
AP
Vrelust
Inge
I
Jorens
Philippe G
PG
Goossens
Herman
H
de Vries
I Jolanda
IJ
Price
David A
DA
Oji
Yusuke
Y
Oka
Yoshihiro
Y
Sugiyama
Haruo
H
Berneman
Zwi N
ZN
D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics; D012074:Remission Induction; D014611:Vaccination; D025721:WT1 Proteins / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D012333:RNA, Messenger; D025721:WT1 Proteins; D007371:Interferon-gamma