Induction of complete and molecular remissions in acute myeloid leukemia by Wilms’ tumor 1 antigen-targeted dendritic cell vaccination
Open accessAbstract
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.
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mRNA vaccines have shown good efficacy in the treatment of acute myelocytic leukemia (AML), non-small cell lung cancer (NSCLC), and melanoma.
“mRNA vaccines have shown good efficacy in the treatment of acute myelocytic leukemia (AML),339–341 non-small cell lung cancer (NSCLC),342,343 and melanoma344–348 (Table 3).”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [339]
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- Authors
- Van Tendeloo, V. F., Van de Velde, A., Van Driessche, A., Cools, N., Anguille, S., Ladell, K., Gostick, E., 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, D. A., Oji, Y., Oka, Y., Sugiyama, H., & Berneman, Z. N.
- Affiliations
- 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;
- University of Antwerp (BE)
- Cardiff University (GB)
- Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, United Kingdom;
- Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen 6525 GA, The Netherlands; and
- The University of Osaka (JP)
- Departments of Molecular Medicine and Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-07-14
- Volume
- 107
- Issue
- 31
- Pages
- 13824-13829
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2922237
- OpenAlex
- W2004037261
- Cited by
- 377
- References
- 63
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 19 · 2023: 14 · 2022: 15 · 2021: 16 · 2020: 20 · 2019: 17 · 2018: 23 · 2017: 27 · 2016: 28 · 2015: 31 · 2014: 30 · 2013: 38 · 2012: 38
- FWCI
- 16.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- European Hematology Association
- Stichting Tegen Kanker
- Universiteit Antwerpen
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- acute myeloid leukemia, WT1, dendritic cell vaccination, autologous dendritic cells, mRNA electroporation, molecular remission, complete remission, CD8+ T cells, natural killer cells, interferon-gamma, post-remission therapy, adjuvant immunotherapy
- MeSH terms
- Antigens, Neoplasm, Dendritic Cells, Humans, Interferon-gamma, Remission Induction, RNA, Messenger, Vaccination, Leukemia, Myeloid, Acute, CD8-Positive T-Lymphocytes, Cancer Vaccines, WT1 Proteins
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