Wilms tumor gene (WT1) mRNA¨Ctransfected autologous dendritic cell vaccination for patients with acute myeloid leukemia. A pilot dose escalation study.
- Conditions
- acute myeloid leukemia
- Registration Number
- NL-OMON27609
- Lead Sponsor
- Antwerp University Hospital, Antwerp, Belgium
- Brief Summary
1. Lion E, Smits EL, Berneman ZN, Van Tendeloo VF. Acute myeloid leukemic cell lines loaded with synthetic dsRNA trigger IFN-gamma secretion by human NK cells. Leukemia Research 2008; Oct 7. [Epub ahead of print] IF 2.561 2. Van de Velde ALR, Berneman ZN, Van Tendeloo VFI. Latest inputs in immunotherapy of hematological malignancies using dendritic cells. Bulletin du Cancer 2008; 95: 320-326 (review) IF 0.906 3. Smits E, Ponsaerts P, Berneman Z, Van Tendeloo VFI. The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy. The Oncologist 2008 (in press). IF 4.876 4. Cools N, Van Tendeloo VFI, Smits ELJM, Lenjou M, Nijs G, Van Bockstaele DR, Berneman ZN, Ponsaerts P. Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells. Journal of Cellular and Molecular Medicine 2008; 12(2): 690-700. IF 6.555 5. Van Gulck ER, Vanham G, Heyndrickx L, Coppens S, Vereecken K, Atkinson D, Florence E, Kint I, Berneman ZN, Van Tendeloo V. Efficient in vitro expansion of HIV-specific T cell responses by gag mRNA-electroporated dendritic cells from treated and untreated HIV-1-infected individuals. J Virol 2008 ;82(7):3561-73. Epub 2008 Jan 30. IF 5.341 6. Van Tendeloo VFI, Ponsaerts P, Berneman ZN. Messenger RNA-based gene therapy as a tool for gene and cell therapy. Current Opinion in Molecular Therapeutics 2007;9(5):423-431 (review) IF 2.411 7. Smits ELJM, Ponsaerts P, Van de Velde ALR, Van Driessche A, Cools N, Lenjou M, Nijs G, Van Bockstaele DR, Berneman ZN, Van Tendeloo VFI. Proinflammatory response of human leukemic cells to dsRNA transfection linked to activation of dendritic cells. Leukemia 2007; 21(8):1691-1699. IF 6.146 8. Bontkes HJ, Kramer D, Ruizendaal JJ, Kueter EWM, Van Tendeloo VFI, Meijer CJLM, Hooijberg E. Dendritic cells transfected with Interleukin-12 and tumor associated antigen mRNA induce high avidity cytotoxic T-cells. Gene Therapy 2007;14(4):366-75 IF 4.836 9. Van Gulck ERA, Ponsaerts P, Heyndrickx L, Vereecken K, Moerman F, De Roo A, Colebunders R, Van den Bosch G, Van Bockstaele DR, Van Tendeloo VFI, Allard S, Verrier B, Marañ¨®n C, Hoeffel G, Hosmalin A, Berneman ZN, Vanham G. Efficient stimulation of HIV-1-specific T-cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env protein. Blood 2006; 107(5): 1818-27. IF 10.131 10. Van Driessche A, Gao L, Stauss HJ, Ponsaerts P, Van Bockstaele DR, Berneman ZN, Van Tendeloo VFI. Antigen-specific cellular immunotherapy of leukemia. Leukemia 2005; 19, 1863¨C1871 (review) IF 6.612 11. Van Driessche A, Ponsaerts P, Van Bockstaele DR, Van Tendeloo VFI, Berneman ZN.Messenger RNA electroporation: An efficient tool in immunotherapy and stem cell research. Folia Histochemica et Cytobiologica 2005, 43(4): 213-216. IF 0.789 12. Ponsaerts P, Van Tendeloo VFI, Berneman ZN. Cancer immunotherapy using RNA-loaded dendritic cells. (review) Clinical and Experimental Immunology 2003; 134: 378-384 IF 2.347 13. Ponsaerts P, Van Tendeloo VFI, Cools N, Van Driessche A, Lardon F, Nijs G, Lenjou M, Van Broeckhoven C, Van Bockstaele DR, Berneman ZN. mRNA-electroporated mature dendritic cells retain transgene expression, phenotypical properties and stimulatory capacity after cryopreservation. Leukemia 2002; 16: 1324-1330 IF 4.693 14. Ponsaerts P, Van den Bosch G, Cools N, Van Driessche A, Nijs G, Lenjou M, Lardon F, Van Broeckhoven C, Van Bockstaele DR, Berneman ZN, Van Tendeloo VFI. Messenger RNA electroporation of human monocytes, followed by rapid in vitro differentiation, leads to highly stimulatory antigen-loaded mature dendritic cells. Journal of Immunology 2002;169:1669-1675. IF 7.014 15. Van Meirvenne S, Straetman L, Heirman C, Dullaers M, De Greef C, Van Tendeloo VFI, Thielemans K. Efficient genetic modification of murine dendritic cells by electroporation with mRNA. Cancer Gene Ther 2002;9:787-97 IF 2.929 16. Van Tendeloo VFI, Ponsaerts P, Lardon F, Lenjou M, Nijs G, Van Broeckhoven C, Van Bockstaele D, Berneman ZN. Highly efficient gene delivery by mRNA electroporation of human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood 2001; 98: 49-56
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
1. Tumor type: Acute Myeloid Leukemia (AML) according to the WHO criteria (ea at least 20% blasts in the marrow). This % should be assessed on a BM aspiration or, in case of dry tap, on a BM biopsy. All FAB subtypes except M3.
Patients with Myelodysplastic Syndrome, category of Refractory Anemia with Excess Blasts (RAEB): RAEB I (WHO: medullary blast count ¡Ü 10% and a peripheral blast count ¡Ü 5%) and RAEB II (WHO: medullary blast count > 10% and/or > 5% peripheral blasts) can be included in the study in absence of other non-experimental treatment modalities.
1. Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix);
2. Subjects who are pregnant;
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety of multiple DC injections. Assessment of acute toxicity and/or auto-immunity.
- Secondary Outcome Measures
Name Time Method Detection of WT1-specific T cell immunity by:<br /><br>1. IFN-gamma ELISPOT;<br /><br>2. WT1 Tetramer analysis (if patient is HLA*A0201 positive);<br /><br>3. DTH skin test;<br /><br><br /><br /><br>Clinical response as evidenced by decreased WT1 RNA levels in peripheral blood measured by quantitative RT-PCR.<br>