33 results on '"Willemen Y"'
Search Results
2. Interferon-α in acute myeloid leukemia: an old drug revisited
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Anguille, S, Lion, E, Willemen, Y, Van Tendeloo, V F I, Berneman, Z N, and Smits, E L J M
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- 2011
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3. Vaccination of cancer patients with dendritic cells electroporated with mRNA encoding the wilms' tumor 1 protein (WT1): correlation of clinical effect and overall survival with T-cell response
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Berneman, Z.N., primary, Anguille, S., additional, Willemen, Y., additional, de Velde, A. Van, additional, Germonpre, P., additional, Huizing, M., additional, Van Tendeloo, V., additional, Saevels, K., additional, Rutsaert, L., additional, Vermeulen, K., additional, Snoeckx, A., additional, de Beeck, B. Op, additional, Cools, N., additional, Nijs, G., additional, Stein, B., additional, Lion, E., additional, Van Driessche, A., additional, Peeters, M., additional, and Smits, E., additional
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- 2019
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4. Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma
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Berneman, Z., primary, Van de Velde, A., additional, Anguille, S., additional, Willemen, Y., additional, Huizing, M., additional, Germonpré, P., additional, Saevels, K., additional, Nijs, G., additional, Cools, N., additional, Van Driessche, A., additional, Stein, B., additional, De Reu, H., additional, Schroyens, W., additional, Gadisseur, A., additional, Verlinden, A., additional, Vermeulen, K., additional, Maes, M., additional, Lammens, M., additional, Goossens, H., additional, Peeters, M., additional, Van Tendeloo, V., additional, and Smits, E., additional
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- 2016
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5. 22 - Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma
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Berneman, Z., Van de Velde, A., Anguille, S., Willemen, Y., Huizing, M., Germonpré, P., Saevels, K., Nijs, G., Cools, N., Van Driessche, A., Stein, B., De Reu, H., Schroyens, W., Gadisseur, A., Verlinden, A., Vermeulen, K., Maes, M., Lammens, M., Goossens, H., Peeters, M., Van Tendeloo, V., and Smits, E.
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- 2016
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6. Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells
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Evelien Smits, Zwi N. Berneman, Eva Lion, Johan M.J. Van den Bergh, Sébastien Anguille, Angela Papagna, Ottavio Beretta, Herman Goossens, Heleen H. Van Acker, Yannick Willemen, Viggo Van Tendeloo, Maria Foti, Lien De Caluwé, Van Acker, H, Beretta, O, Anguille, S, Caluwé, L, Papagna, A, Van den Bergh, J, Willemen, Y, Goossens, H, Berneman, Z, Van Tendeloo, V, Smits, E, Foti, M, and Lion, E
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CD4-Positive T-Lymphocytes ,0301 basic medicine ,Chemokine ,T cell ,Vesicular Transport Proteins ,Gene Expression ,chemical and pharmacologic phenomena ,NK cells ,CD8-Positive T-Lymphocytes ,Immunotherapy, Adoptive ,γδ T cells ,Cell therapy ,03 medical and health sciences ,Immune system ,Cell Movement ,Humans ,Medicine ,CCL4-CCR5 signaling ,Biology ,Interleukin-15 ,biology ,business.industry ,Effector ,immune cell recruitment ,Receptors, Antigen, T-Cell, gamma-delta ,Dendritic Cells ,Dendritic cell ,CCL4-CCR5 signaling, dendritic cell vaccination, γδ T cells, immune cell recruitment, NK cells ,Killer Cells, Natural ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Interleukin 15 ,Immunology ,biology.protein ,dendritic cell vaccination ,Human medicine ,Chemokines ,business ,CD8 ,Research Paper - Abstract
// Heleen H. Van Acker 1 , Ottavio Beretta 2 , Sebastien Anguille 1, 3 , Lien De Caluwe 1, 4 , Angela Papagna 2 , Johan M. Van den Bergh 1 , Yannick Willemen 1 , Herman Goossens 1 , Zwi N. Berneman 1, 3 , Viggo F. Van Tendeloo 1 , Evelien L. Smits 1, 3, 5 , Maria Foti 2, * , Eva Lion 1, 3, * 1 Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium 2 School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy 3 Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium 4 Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 5 Center for Oncological Research (CORE), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium * Share senior authorship Correspondence to: Heleen H. Van Acker, email: heleen.vanacker@uantwerp.be Keywords: CCL4-CCR5 signaling, dendritic cell vaccination, γδ T cells, immune cell recruitment, NK cells Received: April 25, 2016 Accepted: January 03, 2017 Published: January 13, 2017 ABSTRACT Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells. Here, we demonstrate that IL-4 DCs are suboptimal in attracting effector lymphocytes, while IL15 DCs provide a favorable chemokine milieu for recruiting CD8 + T cells, natural killer (NK) cells and gamma delta (γδ) T cells. Gene expression analysis revealed that IL-15 DCs exhibit a high expression of chemokines involved in antitumor immune effector cell attraction, while IL-4 DCs display a more immunoregulatory profile characterized by the expression of Th2 and regulatory T cell-attracting chemokines. This is confirmed by functional data indicating an enhanced recruitment of granzyme B + effector lymphocytes by IL-15 DCs, as compared to IL-4 DCs, and subsequent superior killing of tumor cells by the migrated lymphocytes. Elevated CCL4 gene expression in IL-15 DCs and lowered CCR5 expression on both migrated γδ T cells and NK cells, led to validation of increased CCL4 secretion by IL15 DCs. Moreover, neutralization of CCR5 prior to migration resulted in an important inhibition of γδ T cell and NK cell recruitment by IL-15 DCs. These findings further underscore the strong immunotherapeutic potential of IL-15 DCs.
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- 2017
7. Multimodality imaging for intraprocedural guidance of a transcatheter tricuspid valve replacement.
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Willemen Y, Møller JE, Nejjari M, Linde JJ, Vejlstrup NG, von Bardeleben RS, Latib A, Modine T, and De Backer O
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- Humans, Tricuspid Valve Insufficiency diagnostic imaging, Tricuspid Valve Insufficiency surgery, Tricuspid Valve diagnostic imaging, Tricuspid Valve surgery, Male, Female, Treatment Outcome, Echocardiography, Transesophageal methods, Aged, Heart Valve Prosthesis Implantation methods, Multimodal Imaging methods, Cardiac Catheterization methods
- Abstract
Competing Interests: Conflict of interest: A.L. is a consultant for VDyne and Shifamed. T.M. received consulting fees from JensCare Scientific. The other authors have no relationships relevant to the contents of this paper to disclose.
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- 2024
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8. Transcatheter Aortic Valve Implantation in Low-Risk Tricuspid or Bicuspid Aortic Stenosis: The NOTION-2 Trial.
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Jørgensen TH, Thyregod HGH, Savontaus M, Willemen Y, Bleie Ø, Tang M, Niemela M, Angerås O, Gudmundsdóttir IJ, Sartipy U, Dagnegaard H, Laine M, Rück A, Piuhola J, Petursson P, Christiansen EH, Malmberg M, Olsen PS, Haaverstad R, Sondergaard L, and De Backer O
- Abstract
Background and Aims: Transcatheter aortic valve implantation (TAVI) has become the first choice to treat older patients with severe symptomatic aortic stenosis (AS). This study aimed to compare TAVI with surgery in low-risk patients ≤ 75 years of age, including both tricuspid and bicuspid AS., Methods: The NOTION-2 trial enrolled and 1:1 randomized low-risk patients aged ≤ 75 years with severe symptomatic AS to TAVI or surgery. The primary endpoint was a composite of all-cause mortality, stroke or rehospitalization (related to the procedure, valve or heart failure) at 12 months., Results: A total of 370 patients were enrolled with a mean age of 71.1 years and a median Society of Thoracic Surgeons risk score of 1.1%. A total of 100 patients had bicuspid AS. The 1-year incidence of the primary endpoint was 10.2% in the TAVI group and 7.1% in the surgery group (absolute risk difference 3.1%; 95% confidence interval [CI], -2.7% to 8.8%; hazard ratio (HR) 1.4, 95% CI: 0.7 to 2.9; p=0.3). Patients with TAVI, when compared to surgery, had lower risk of major bleeding and new-onset atrial fibrillation and higher risk of non-disabling stroke, permanent pacemaker implantation and moderate-or-greater paravalvular regurgitation. The risk of the primary composite endpoint was 8.7% and 8.3% in patients with tricuspid AS (HR 1.0, 95% CI: 0.5 to 2.3) and 14.3% and 3.9% in patients with bicuspid AS (HR 3.8, 95% CI: 0.8 to 18.5) treated with TAVI or surgery, respectively (P for interaction=0.1)., Conclusions: Among low-risk patients aged ≤ 75 years with severe symptomatic AS, the rate of the composite of death, stroke, or rehospitalization at one year was similar between TAVI and surgery. TAVI outcomes in young bicuspid AS patients warrant caution and should be further investigated. (NOTION-2, ClinicalTrials.gov, NCT02825134)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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9. Outcomes and predictors of left ventricle recovery in patients with severe left ventricular dysfunction undergoing transcatheter aortic valve implantation.
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Witberg G, Levi A, Talmor-Barkan Y, Barbanti M, Valvo R, Costa G, Frittitta V, de Backer O, Willemen Y, van Der Dorpel M, Mon M, Sugiura A, Sudo M, Masiero G, Pancaldi E, Arzamendi D, Santos-Martinez S, Baz JA, Steblovnik K, Mauri V, Adam M, Wienemann H, Zahler D, Hein M, Ruile P, Aodha BN, Grasso C, Branca L, Estévez-Loureiro R, Amat-Santos IJ, Mylotte D, Bunc M, Tarantini G, Nombela-Franco L, Sondergaard L, Van Mieghem NM, Finkelstein A, and Kornowski R
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- Humans, Aortic Valve surgery, Heart Ventricles, Stroke Volume, Treatment Outcome, Ventricular Function, Left, Multicenter Studies as Topic, Clinical Studies as Topic, Aortic Valve Stenosis, Transcatheter Aortic Valve Replacement adverse effects, Ventricular Dysfunction, Left
- Abstract
Background: Data on the likelihood of left ventricle (LV) recovery in patients with severe LV dysfunction and severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and its prognostic value are limited., Aims: We aimed to assess the likelihood of LV recovery following TAVI, examine its association with midterm mortality, and identify independent predictors of LV function., Methods: In our multicentre registry of 17 TAVI centres in Western Europe and Israel, patients were stratified by baseline LV function (ejection fraction [EF] >/≤30%) and LV response: no LV recovery, LV recovery (EF increase ≥10%), and LV normalisation (EF ≥50% post-TAVI)., Results: Our analysis included 10,872 patients; baseline EF was ≤30% in 914 (8.4%) patients and >30% in 9,958 (91.6%) patients. The LV recovered in 544 (59.5%) patients, including 244 (26.7%) patients whose LV function normalised completely (EF >50%). Three-year mortality for patients without severe LV dysfunction at baseline was 29.4%. Compared to this, no LV recovery was associated with a significant increase in mortality (adjusted hazard ratio 1.32; p<0.001). Patients with similar LV function post-TAVI had similar rates of 3-year mortality, regardless of their baseline LV function. Three variables were associated with a higher likelihood of LV recovery following TAVI: no previous myocardial infarction (MI), estimated glomerular filtration rate >60 mL/min, and mean aortic valve gradient (mAVG) (expressed either as a continuous variable or as a binary variable using the standard low-flow, low-gradient aortic stenosis [AS] definition)., Conclusions: LV recovery following TAVI and the extent of this recovery are major determinants of midterm mortality in patients with severe AS and severe LV dysfunction undergoing TAVI. Patients with no previous MI and those with an mAVG >40 mmHg show the best results following TAVI, which are at least equivalent to those for patients without severe LV dysfunction. (ClinicalTrials.gov: NCT04031274).
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- 2024
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10. Stroke prevention in TAVR: A patient-tailored approach may be needed.
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Willemen Y and De Backer O
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- Humans, Treatment Outcome, Aortic Valve diagnostic imaging, Aortic Valve surgery, Risk Factors, Transcatheter Aortic Valve Replacement adverse effects, Aortic Valve Stenosis diagnostic imaging, Aortic Valve Stenosis surgery, Stroke etiology, Stroke prevention & control
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- 2023
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11. Orbital atherectomy to facilitate transfemoral transcatheter aortic valve implantation in patients with calcified iliofemoral arteries: a case series.
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Quagliana A, Montarello NJ, Vanhaverbeke M, Willemen Y, Campens L, Sondergaard L, and De Backer O
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Background: The transfemoral (TF) approach drives most of the advantages of transcatheter aortic valve implantation (TAVI) over surgical aortic valve replacement. Alternative accesses for TAVI are associated with higher complication rates, but are still considered in ∼5% of cases due to peripheral arterial disease (PAD). Percutaneous transluminal angioplasty can still allow TF-TAVI in selected cases with severe calcific PAD; however, ancillary techniques for calcium management are often needed., Case Summary: Orbital atherectomy was selected to facilitate TF-TAVI in two patients with different degrees and aspects of calcific PAD. Pre-procedural computed tomography analysis was key to choose the most appropriate technique for calcium management. We describe our experience with a step-by-step procedural approach to orbital atherectomy-assisted TF-TAVI., Discussion: PAD is not uncommon in patients affected by severe symptomatic aortic valve stenosis. Orbital atherectomy can still allow TF-TAVI in selected cases with severe calcific PAD. A meticulous patient selection and a standardized, step-wise procedural execution are mandatory to optimize outcomes., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2023
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12. Transcatheter aortic valve durability: a contemporary clinical review.
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Montarello NJ, Willemen Y, Tirado-Conte G, Travieso A, Bieliauskas G, Sondergaard L, and De Backer O
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Encouraged by randomized controlled trials demonstrating non-inferiority of transfemoral transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) across all surgical risk categories, there has been a dramatic increase in the use of TAVI in a younger patient cohort with severe aortic stenosis, endorsed by both European and American Cardiac Societies. However, the standard use of TAVI in younger, less co-morbid patients with a longer life expectancy can only be supported if there is sound data demonstrating long-term durability of transcatheter aortic valves (TAVs). In this article, we have reviewed available randomized and observational registry clinical data pertaining to TAV long-term durability, placing emphasis on trials and registries using the new standardized definitions of bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF). Despite inherent difficulties in interpreting the available data, the determination reached is that the risk of structural valve deterioration (SVD) is potentially lower after TAVI than SAVR at 5 to 10 years, and that the two treatment modalities have a similar risk of BVF. This supports the adoption of TAVI in younger patients evident in current practice. However, the routine use of TAVI in younger patients with bicuspid aortic valve stenosis should be cautioned due to insufficient long-term TAV durability data in this particular patient population. Finally, we highlight the importance of future research into the unique potential mechanisms that can potentially contribute to TAV degeneration., Competing Interests: GB, LS and ODB received institutional research grants and consulting fees from Abbott, Boston Scientific, and Medtronic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Montarello, Willemen, Tirado-Conte, Travieso, Bieliauskas, Sondergaard and De Backer.)
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- 2023
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13. In vitro expansion of Wilms' tumor protein 1 epitope-specific primary T cells from healthy human peripheral blood mononuclear cells.
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van der Heijden S, Flumens D, Versteven M, Peeters S, Reu H, Campillo-Davo D, Willemen Y, Ogunjimi B, Van Tendeloo V, Berneman ZN, Anguille S, Smits E, and Lion E
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- Humans, Epitopes, Leukocytes, Mononuclear, T-Lymphocytes, Cytotoxic, Wilms Tumor metabolism, Kidney Neoplasms metabolism
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Wilms' tumor protein 1 (WT1) is a tumor-associated antigen overexpressed in various cancers. As a self-antigen, negative selection reduces the number of WT1-specific T cell receptors (TCRs). Here, we provide a protocol to generate WT1
37-45 -specific TCRs using healthy human peripheral blood mononuclear cells. We describe the expansion of WT1-specific T cell clones by two consecutive in vitro stimulations with autologous WT137-45 -pulsed dendritic cells and peripheral blood lymphocytes. We then detail the detection with human leukocyte antigen/WT137-45 tetramers., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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14. Commissural Alignment and Coronary Access after Transcatheter Aortic Valve Replacement.
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Quagliana A, Montarello NJ, Willemen Y, Bække PS, Jørgensen TH, De Backer O, and Sondergaard L
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Transcatheter aortic valve implantation (TAVR) is the first therapeutic option for elderly patients with severe symptomatic aortic stenosis, and indications are steadily expanding to younger patients and subjects with lower surgical risk and longer life expectancy. Commissural alignment between native and transcatheter valves facilitates coronary access after TAVR and is thus considered a procedural goal, allowing long-term management of coronary artery disease. Moreover, commissural alignment may potentially have a positive impact on transvalvular hemodynamic and valve durability. This review focus on technical hints to achieve commissural alignment and current evidence for different transcatheter aortic valves.
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- 2023
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15. Feasibility, safety and predictors of a successful "blind wiring" antegrade approach in the percutaneous treatment of chronic coronary total occlusions.
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Vescovo GM, Somov P, Zivelonghi C, Bezzeccheri A, Scott B, Wilgenhof A, Willemen Y, Convens C, Verheye S, Vermeersch P, and Agostoni P
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- Humans, Retrospective Studies, Feasibility Studies, Percutaneous Coronary Intervention adverse effects, Coronary Occlusion diagnostic imaging, Coronary Occlusion surgery, Heart Injuries
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Background: Antegrade wiring using only antegrade guiding catheter without contralateral injection (defined as "blind antegrade wiring") may represent a valid initial treatment strategy for selected chronic coronary total occlusions (CTOs) due to the potentially lower risk of vascular complications. A careful selection of lesions eligible for this strategy as well as an accurate balance between the likelihood of success and failure is paramount. The aim of the study is to determine the rate of successful revascularization, the potential predictors of failure and the incidence of major complications, when using a "blind antegrade wiring" technique., Methods: In this multicentric study, consecutive patients with CTO undergoing percutaneous coronary intervention (PCI) were retrospectively screened. All cases approached using "blind antegrade wiring" technique were included., Results: Out of 155 consecutive CTO-PCIs, 94 involved initial "blind antegrade wiring" strategy. Successful revascularization by means of "blind antegrade wiring" technique was achieved in 73 (78%) patients. Final successful revascularization was obtained in 19 of the remaining 21 procedures with "blind antegrade wiring" failure using other techniques (by adding a second contralateral guiding catheter; 98% total successful revascularization). Logistic regression analysis identified higher J-CTO Score as the only predictor of "blind antegrade wiring" failure. One complication occurred (wire-based coronary perforation)., Conclusions: "Blind antegrade wiring" may be considered as initial strategy for selected CTO-PCI, mainly for CTOs with low J-CTO Score. This strategy would allow in a substantial number of cases to avoid a priori dual injection, keeping it as secondary strategy in case of "blind antegrade wiring" failure.
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- 2023
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16. Trends and outcomes in transcatheter aortic valve implantation in Belgium: a 13-year single centre experience.
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Bezzeccheri A, Vermeersch P, Verheye S, Wilgenhof A, Willemen Y, Vescovo GM, Scott B, Convens C, Zivelonghi C, and Agostoni P
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- Humans, Belgium epidemiology, Retrospective Studies, Risk Factors, Treatment Outcome, Aortic Valve surgery, Transcatheter Aortic Valve Replacement adverse effects, Aortic Valve Stenosis diagnosis, Aortic Valve Stenosis surgery, Heart Valve Prosthesis Implantation methods
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Background: Transcatheter aortic valve implantation (TAVI) has been adopted as an alternative to surgery in severe aortic stenosis treatment, even in low-intermediate risk. The aim of this study is to retrospectively report our single-centre 13-year TAVI experience with emphasis on learning curve, referral indication and trends in outcomes over time., Methods: We included 361 consecutive patients who underwent TAVI from January 2008 to December 2020, grouped according to similar per-year volume of procedures: G1 (2008-2014), G2 (2015-2017) and G3 (2018-2020)., Results: The number of procedures increased (group size: 59 vs . 106 vs . 196). No major differences were observed in STS-PROM and EuroSCORE-II between groups, despite TAVI in patients with prior surgical revascularisation was mainly performed in G1. Trans-femoral approach raised from 80.8 to 93.4%, while the most common alternative access was trans-subclavian. The pre-dilation rate was higher in G1 with lower prosthesis post-dilation rate. The length of hospital stay decreased in time by 30%. At 30 days a reduction in all-cause mortality, vascular complications, bleedings and para-valvular leak combined with higher rate of permanent pacing were observed over the groups. At 1-year there was no difference in all-cause mortality but over 30% reduction in cardiovascular death (8.5 vs. 7.5 vs. 5.6%)., Conclusions: Favourable trends were observed across the groups, with an improvement in periprocedural outcomes and cardiovascular mortality at 1-year. These improvements could depend on increased expertise because mortality reduction was noted only after reaching a significant procedure volume. A trend towards lower risk patients selection was present in our cohort, as previously described worldwide.
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- 2022
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17. Very long-term outcome of saphenous vein graft percutaneous coronary intervention: bare-metal stent versus sirolimus-eluting stent.
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Zivelonghi C, Vescovo GM, Agostoni P, Wilgenhof A, Willemen Y, Scott B, Convens C, Verheye S, and Vermeersch P
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- Graft Occlusion, Vascular diagnostic imaging, Graft Occlusion, Vascular etiology, Graft Occlusion, Vascular therapy, Humans, Prosthesis Design, Saphenous Vein diagnostic imaging, Saphenous Vein transplantation, Sirolimus, Stents, Treatment Outcome, Drug-Eluting Stents, Percutaneous Coronary Intervention adverse effects
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- 2022
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18. Comparison of Different Stenting Techniques in Left Main Bifurcation Disease: Evidence From a Network Meta-Analysis.
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Vescovo GM, Chiabrando JG, Zivelonghi C, Romeo FJ, Lombardi M, Del Buono MG, Galli M, Biondi-Zoccai G, Wilgenhof A, Willemen Y, Scott B, Convens C, Verheye S, Vermeersch P, and Agostoni P
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- Humans, Network Meta-Analysis, Stents, Treatment Outcome, Coronary Artery Disease diagnosis, Coronary Artery Disease surgery, Percutaneous Coronary Intervention adverse effects, Percutaneous Coronary Intervention methods
- Abstract
Objectives: We aimed to assess which bifurcation technique performs best in unprotected left-main (LM) percutaneous coronary intervention (PCI)., Background: Provisional stenting was considered the preferred technique for LM bifurcation PCI due to the supposed lower risks of thrombosis and restenosis. However, recent studies showed potential advantages of double kissing (DK)-crush technique over the other strategies., Methods: We performed a frequentist network meta-analysis comparing different stenting techniques in the setting of LM bifurcation. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were searched. Both randomized clinical trials and non-randomized clinical trials were considered eligible for inclusion. Incidence rate ratios (IRRs) were computed using a random-effects model for death, cardiac death, myocardial infarction, target-vessel revascularization, target-lesion revascularization, and stent thrombosis, including 95% confidence intervals (CIs)., Results: A total of 10 studies (2364 patients) were included. Compared with provisional stenting, DK-crush was associated with fewer cardiac deaths (IRR, 0.34; 95% CI, 0.17-0.70; P<.01), myocardial infarctions (IRR, 0.19; 95% CI, 0.08-0.44; P<.001), stent thromboses (IRR, 0.31; 95% CI, 0.14-0.69; P<.01), target-vessel revascularizations (IRR, 0.25; 95% CI, 0.14-0.46; P<.001), and target-lesion revascularizations (IRR, 0.25; 95% CI, 0.14-0.46; P<.001). DK-crush was also associated with a lower risk of myocardial infarction (IRR, 0.19; 95% CI, 0.05-0.76; P=.02) when compared with standard crush and lower risk of target-lesion revascularization when compared with culotte (IRR, 0.32; 95% CI, 0.12-0.83; P=.02) and crush (IRR, 0.07; 95% CI, 0.02-0.28; P<.001)., Conclusions: DK-crush is the best technique for unprotected LM bifurcation PCI.
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- 2022
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19. Left Ventricular Free Wall Rupture During Ventriculography.
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Willemen Y, Zivelonghi C, Vermeersch P, and Scott B
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- Aged, Cardiac Surgical Procedures, Cardiopulmonary Resuscitation, Female, Heart Rupture, Post-Infarction etiology, Heart Rupture, Post-Infarction therapy, Humans, Inferior Wall Myocardial Infarction complications, Predictive Value of Tests, ST Elevation Myocardial Infarction complications, Treatment Outcome, Heart Rupture, Post-Infarction diagnostic imaging, Inferior Wall Myocardial Infarction diagnostic imaging, Radionuclide Ventriculography, ST Elevation Myocardial Infarction diagnostic imaging
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- 2020
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20. Ribonucleic Acid Engineering of Dendritic Cells for Therapeutic Vaccination: Ready 'N Able to Improve Clinical Outcome?
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Willemen Y, Versteven M, Peeters M, Berneman ZN, and Smits ELJ
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Targeting and exploiting the immune system has become a valid alternative to conventional options for treating cancer and infectious disease. Dendritic cells (DCs) take a central place given their role as key orchestrators of immunity. Therapeutic vaccination with autologous DCs aims to stimulate the patient's own immune system to specifically target his/her disease and has proven to be an effective form of immunotherapy with very little toxicity. A great amount of research in this field has concentrated on engineering these DCs through ribonucleic acid (RNA) to improve vaccine efficacy and thereby the historically low response rates. We reviewed in depth the 52 clinical trials that have been published on RNA-engineered DC vaccination, spanning from 2001 to date and reporting on 696 different vaccinated patients. While ambiguity prevents reliable quantification of effects, these trials do provide evidence that RNA-modified DC vaccination can induce objective clinical responses and survival benefit in cancer patients through stimulation of anti-cancer immunity, without significant toxicity. Succinct background knowledge of RNA engineering strategies and concise conclusions from available clinical and recent preclinical evidence will help guide future research in the larger domain of DC immunotherapy., Competing Interests: The authors declare no conflict of interest. The funders had no role in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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- 2020
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21. Poly(I:C) primes primary human glioblastoma cells for an immune response invigorated by PD-L1 blockade.
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De Waele J, Marcq E, Van Audenaerde JR, Van Loenhout J, Deben C, Zwaenepoel K, Van de Kelft E, Van der Planken D, Menovsky T, Van den Bergh JM, Willemen Y, Pauwels P, Berneman ZN, Lardon F, Peeters M, Wouters A, and Smits EL
- Abstract
Prognosis of glioblastoma remains dismal, underscoring the need for novel therapies. Immunotherapy is generating promising results, but requires combination strategies to unlock its full potential. We investigated the immunomodulatory capacities of poly(I:C) on primary human glioblastoma cells and its combinatorial potential with programmed death ligand (PD-L) blockade. In our experiments, poly(I:C) stimulated expression of both PD-L1 and PD-L2 on glioblastoma cells, and a pro-inflammatory secretome, including type I interferons (IFN) and chemokines CXCL9, CXCL10, CCL4 and CCL5. IFN-β was partially responsible for the elevated PD-1 ligand expression on these cells. Moreover, real-time PCR and chloroquine-mediated blocking experiments indicated that poly(I:C) triggered Toll-like receptor 3 to elicit its effect. Cocultures of poly(I:C)-treated glioblastoma cells with peripheral blood mononuclear cells enhanced lymphocytic activation (CD69, IFN-γ) and cytotoxic capacity (CD107a, granzyme B). Additional PD-L1 blockade further propagated immune activation. Besides activating immunity, poly(I:C)-treated glioblastoma cells also doubled the attraction of CD8
+ T cells, and to a lesser extent CD4+ T cells, via a mechanism which included CXCR3 and CCR5 ligands. Our results indicate that by triggering glioblastoma cells, poly(I:C) primes the tumor microenvironment for an immune response. Secreted cytokines allow for immune activation while chemokines attract CD8+ T cells to the front, which are postulated as a prerequisite for effective PD-1/PD-L1 blockade. Accordingly, additional blockade of the concurrently elevated tumoral PD-L1 further reinforces the immune activation. In conclusion, our data proposes poly(I:C) treatment combined with PD-L1 blockade to invigorate the immune checkpoint inhibition response in glioblastoma.- Published
- 2017
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22. Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells.
- Author
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Van Acker HH, Beretta O, Anguille S, De Caluwé L, Papagna A, Van den Bergh JM, Willemen Y, Goossens H, Berneman ZN, Van Tendeloo VF, Smits EL, Foti M, and Lion E
- Subjects
- CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cell Movement immunology, Chemokines genetics, Chemokines immunology, Gene Expression, Humans, Receptors, Antigen, T-Cell, gamma-delta immunology, Vesicular Transport Proteins immunology, Dendritic Cells immunology, Immunotherapy, Adoptive methods, Interleukin-15 immunology, Killer Cells, Natural immunology
- Abstract
Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells. Here, we demonstrate that IL-4 DCs are suboptimal in attracting effector lymphocytes, while IL15 DCs provide a favorable chemokine milieu for recruiting CD8+ T cells, natural killer (NK) cells and gamma delta (γδ) T cells. Gene expression analysis revealed that IL-15 DCs exhibit a high expression of chemokines involved in antitumor immune effector cell attraction, while IL-4 DCs display a more immunoregulatory profile characterized by the expression of Th2 and regulatory T cell-attracting chemokines. This is confirmed by functional data indicating an enhanced recruitment of granzyme B+ effector lymphocytes by IL-15 DCs, as compared to IL-4 DCs, and subsequent superior killing of tumor cells by the migrated lymphocytes. Elevated CCL4 gene expression in IL-15 DCs and lowered CCR5 expression on both migrated γδ T cells and NK cells, led to validation of increased CCL4 secretion by IL15 DCs. Moreover, neutralization of CCR5 prior to migration resulted in an important inhibition of γδ T cell and NK cell recruitment by IL-15 DCs. These findings further underscore the strong immunotherapeutic potential of IL-15 DCs.
- Published
- 2017
- Full Text
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23. The tumor-associated antigen RHAMM (HMMR/CD168) is expressed by monocyte-derived dendritic cells and presented to T cells.
- Author
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Willemen Y, Van den Bergh JM, Bonte SM, Anguille S, Heirman C, Stein BM, Goossens H, Kerre T, Thielemans K, Peeters M, Van Tendeloo VF, Smits EL, and Berneman ZN
- Subjects
- Cancer Vaccines immunology, Electroporation, Extracellular Matrix Proteins genetics, Gene Expression, HLA-A Antigens immunology, Humans, Hyaluronan Receptors genetics, Immunotherapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute therapy, Neoplasms genetics, Neoplasms immunology, Neoplasms metabolism, Neoplasms therapy, RNA, Messenger genetics, RNA, Messenger metabolism, T-Lymphocytes metabolism, Antigen Presentation immunology, Antigens, Neoplasm immunology, Dendritic Cells immunology, Dendritic Cells metabolism, Extracellular Matrix Proteins immunology, Hyaluronan Receptors immunology, T-Lymphocytes immunology
- Abstract
We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation. Moreover, we found that RHAMM-specific T cells are present at vaccination sites in AML patients. Our findings implicate that we and others who are using classical mo-DCs for cancer immunotherapy are already vaccinating against RHAMM.
- Published
- 2016
- Full Text
- View/download PDF
24. Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor effector functions of human gamma delta T cells.
- Author
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Van Acker HH, Anguille S, Willemen Y, Van den Bergh JM, Berneman ZN, Lion E, Smits EL, and Van Tendeloo VF
- Abstract
Background: Adoptive immunotherapy is gaining momentum to fight malignancies, whereby γδ T cells have received recent attention as an alternative cell source as to natural killer cells and αβ T cells. The advent of γδ T cells is largely due to their ability to recognize and target tumor cells using both innate characteristic and T cell receptor (TCR)-mediated mechanisms, their capacity to enhance the generation of antigen-specific T cell responses, and their potential to be used in an autologous or allogeneic setting., Methods: In this study, we explored the beneficial effect of the immunostimulatory cytokine interleukin (IL)-15 on purified γδ T cells and its use as a stimulatory signal in the ex vivo expansion of γδ T cells for adoptive transfer. The expansion protocol was validated both with immune cells of healthy individuals and acute myeloid leukemia patients., Results: We report that the addition of IL-15 to γδ T cell cultures results in a more activated phenotype, a higher proliferative capacity, a more pronounced T helper 1 polarization, and an increased cytotoxic capacity of γδ T cells. Moreover γδ T cell expansion starting with peripheral blood mononuclear cells from healthy individuals and acute myeloid leukemia patients is boosted in the presence of IL-15, whereby the antitumor properties of the γδ T cells are strengthened as well., Conclusions: Our results support the rationale to explore the use of IL-15 in clinical adoptive therapy protocols exploiting γδ T cells.
- Published
- 2016
- Full Text
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25. Bisphosphonates for cancer treatment: Mechanisms of action and lessons from clinical trials.
- Author
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Van Acker HH, Anguille S, Willemen Y, Smits EL, and Van Tendeloo VF
- Subjects
- Animals, Apoptosis drug effects, Cell Adhesion drug effects, Clinical Trials as Topic, Humans, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Diphosphonates pharmacology, Diphosphonates therapeutic use, Neoplasms drug therapy
- Abstract
A growing body of evidence points toward an important anti-cancer effect of bisphosphonates, a group of inexpensive, safe, potent, and long-term stable pharmacologicals that are widely used as osteoporosis drugs. To date, they are already used in the prevention of complications of bone metastases. Because the bisphosphonates can also reduce mortality in among other multiple myeloma, breast, and prostate cancer patients, they are now thoroughly studied in oncology. In particular, the more potent nitrogen-containing bisphosphonates have the potential to improve prognosis. The first part of this review will elaborate on the direct and indirect anti-tumoral effects of bisphosphonates, including induction of tumor cell apoptosis, inhibition of tumor cell adhesion and invasion, anti-angiogenesis, synergism with anti-neoplastic drugs, and enhancement of immune surveillance (e.g., through activation of γδ T cells and targeting macrophages). In the second part, we shed light on the current clinical position of bisphosphonates in the treatment of hematological and solid malignancies, as well as on ongoing and completed clinical trials investigating the therapeutic effect of bisphosphonates in cancer. Based on these recent data, the role of bisphosphonates is expected to further expand in the near future outside the field of osteoporosis and to open up new avenues in the treatment of malignancies., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2016
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26. Generation and Cryopreservation of Clinical Grade Wilms' Tumor 1 mRNA-Loaded Dendritic Cell Vaccines for Cancer Immunotherapy.
- Author
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Smits EL, Stein B, Nijs G, Lion E, Van Tendeloo VF, Willemen Y, Anguille S, and Berneman ZN
- Subjects
- Cells, Cultured, Electroporation, Humans, Vaccination, WT1 Proteins genetics, Cancer Vaccines, Cryopreservation, Dendritic Cells, RNA, Messenger, Wilms Tumor therapy
- Abstract
First described in the 1970s, dendritic cells (DC) are currently subjects of intense investigation to exploit their unique antigen-presenting and immunoregulatory capacities. In cancer, DC show promise to elicit or amplify immune responses directed against cancer cells by activating natural killer (NK) cells and tumor antigen-specific T cells. Wilms' tumor 1 (WT1) protein is a tumor-associated antigen that is expressed in a majority of cancer types and has been designated as an antigen of major interest to be targeted in clinical cancer immunotherapy trials. In this chapter, we describe the generation, cryopreservation, and thawing of clinical grade autologous monocyte-derived DC vaccines that are loaded with WT1 by messenger RNA (mRNA) electroporation. This in-house-developed transfection method gives rise to presentation of multiple antigen epitopes and can be used for all patients without restriction of human leukocyte antigen (HLA) type.
- Published
- 2016
- Full Text
- View/download PDF
27. Transpresentation of interleukin-15 by IL-15/IL-15Rα mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity.
- Author
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Van den Bergh J, Willemen Y, Lion E, Van Acker H, De Reu H, Anguille S, Goossens H, Berneman Z, Van Tendeloo V, and Smits E
- Subjects
- Cancer Vaccines immunology, Coculture Techniques, Cytotoxicity, Immunologic, Dendritic Cells immunology, Dendritic Cells transplantation, Electroporation, Genetic Engineering, Granzymes metabolism, Humans, Interferon-gamma metabolism, Interleukin-15 genetics, K562 Cells, Killer Cells, Natural immunology, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute immunology, Perforin metabolism, Phenotype, RNA, Messenger genetics, Receptors, Interleukin-15 genetics, Remission Induction, Signal Transduction, Time Factors, Transfection, Cell Communication, Dendritic Cells metabolism, Immunotherapy, Adoptive methods, Interleukin-15 metabolism, Killer Cells, Natural metabolism, Leukemia, Myeloid, Acute therapy, Lymphocyte Activation, RNA, Messenger metabolism, Receptors, Interleukin-15 metabolism
- Abstract
In cancer immunotherapy, the use of dendritic cell (DC)-based vaccination strategies can improve overall survival, but until now durable clinical responses remain scarce. To date, DC vaccines are designed primarily to induce effective T-cell responses, ignoring the antitumor activity potential of natural killer (NK) cells. Aiming to further improve current DC vaccination outcome, we engineered monocyte-derived DC to produce interleukin (IL)-15 and/or IL-15 receptor alpha (IL-15Rα) using mRNA electroporation. The addition of IL-15Rα to the protocol, enabling IL-15 transpresentation to neighboring NK cells, resulted in significantly better NK-cell activation compared to IL-15 alone. Next to upregulation of NK-cell membrane activation markers, IL-15 transpresentation resulted in increased NK-cell secretion of IFN-γ, granzyme B and perforin. Moreover, IL-15-transpresenting DC/NK cell cocultures from both healthy donors and acute myeloid leukemia (AML) patients in remission showed markedly enhanced cytotoxic activity against NK cell sensitive and resistant tumor cells. Blocking IL-15 transpresentation abrogated NK cell-mediated cytotoxicity against tumor cells, pointing to a pivotal role of IL-15 transpresentation by IL-15Rα to exert its NK cell-activating effects. In conclusion, we report an attractive approach to improve antitumoral NK-cell activity in DC-based vaccine strategies through the use of IL-15/IL-15Rα mRNA-engineered designer DC.
- Published
- 2015
- Full Text
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28. Engineering monocyte-derived dendritic cells to secrete interferon-α enhances their ability to promote adaptive and innate anti-tumor immune effector functions.
- Author
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Willemen Y, Van den Bergh JM, Lion E, Anguille S, Roelandts VA, Van Acker HH, Heynderickx SD, Stein BM, Peeters M, Figdor CG, Van Tendeloo VF, de Vries IJ, Adema GJ, Berneman ZN, and Smits EL
- Subjects
- Antigens, Neoplasm genetics, CD4-Positive T-Lymphocytes immunology, Cell Proliferation genetics, Cells, Cultured, Dendritic Cells cytology, Dendritic Cells transplantation, Electroporation, Humans, Immunotherapy, Adoptive, Interferon-alpha genetics, Killer Cells, Natural immunology, Lymphocyte Activation immunology, Neoplasms immunology, RNA, Messenger administration & dosage, RNA, Messenger genetics, WT1 Proteins genetics, Antigens, Neoplasm immunology, CD8-Positive T-Lymphocytes immunology, Dendritic Cells immunology, Interferon-alpha metabolism, WT1 Proteins immunology
- Abstract
Dendritic cell (DC) vaccination has demonstrated potential in clinical trials as a new effective cancer treatment, but objective and durable clinical responses are confined to a minority of patients. Interferon (IFN)-α, a type-I IFN, can bolster anti-tumor immunity by restoring or increasing the function of DCs, T cells and natural killer (NK) cells. Moreover, type-I IFN signaling on DCs was found to be essential in mice for tumor rejection by the innate and adaptive immune system. Targeted delivery of IFN-α by DCs to immune cells could boost the generation of anti-tumor immunity, while avoiding the side effects frequently associated with systemic administration. Naturally circulating plasmacytoid DCs, major producers of type-I IFN, were already shown capable of inducing tumor antigen-specific T cell responses in cancer patients without severe toxicity, but their limited number complicates their use in cancer vaccination. In the present work, we hypothesized that engineering easily generated human monocyte-derived mature DCs to secrete IFN-α using mRNA electroporation enhances their ability to promote adaptive and innate anti-tumor immunity. Our results show that IFN-α mRNA electroporation of DCs significantly increases the stimulation of tumor antigen-specific cytotoxic T cell as well as anti-tumor NK cell effector functions in vitro through high levels of IFN-α secretion. Altogether, our findings mark IFN-α mRNA-electroporated DCs as potent inducers of both adaptive and innate anti-tumor immunity and pave the way for clinical trial evaluation in cancer patients.
- Published
- 2015
- Full Text
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29. Interleukin-15 Dendritic Cells Harness NK Cell Cytotoxic Effector Function in a Contact- and IL-15-Dependent Manner.
- Author
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Anguille S, Van Acker HH, Van den Bergh J, Willemen Y, Goossens H, Van Tendeloo VF, Smits EL, Berneman ZN, and Lion E
- Subjects
- CD56 Antigen metabolism, Cell Communication, Cell Line, Tumor, Coculture Techniques, Cytokines metabolism, Humans, Immunotherapy, Lymphocyte Activation, Dendritic Cells immunology, Dendritic Cells metabolism, Interleukin-15 metabolism, Killer Cells, Natural immunology, Killer Cells, Natural metabolism
- Abstract
The contribution of natural killer (NK) cells to the treatment efficacy of dendritic cell (DC)-based cancer vaccines is being increasingly recognized. Much current efforts to optimize this form of immunotherapy are therefore geared towards harnessing the NK cell-stimulatory ability of DCs. In this study, we investigated whether generation of human monocyte-derived DCs with interleukin (IL)-15 followed by activation with a Toll-like receptor stimulus endows these DCs, commonly referred to as "IL-15 DCs", with the capacity to stimulate NK cells. In a head-to-head comparison with "IL-4 DCs" used routinely for clinical studies, IL-15 DCs were found to induce a more activated, cytotoxic effector phenotype in NK cells, in particular in the CD56bright NK cell subset. With the exception of GM-CSF, no significant enhancement of cytokine/chemokine secretion was observed following co-culture of NK cells with IL-15 DCs. IL-15 DCs, but not IL-4 DCs, promoted NK cell tumoricidal activity towards both NK-sensitive and NK-resistant targets. This effect was found to require cell-to-cell contact and to be mediated by DC surface-bound IL-15. This study shows that DCs can express a membrane-bound form of IL-15 through which they enhance NK cell cytotoxic function. The observed lack of membrane-bound IL-15 on "gold-standard" IL-4 DCs and their consequent inability to effectively promote NK cell cytotoxicity may have important implications for the future design of DC-based cancer vaccine studies.
- Published
- 2015
- Full Text
- View/download PDF
30. Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs.
- Author
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Ammi R, De Waele J, Willemen Y, Van Brussel I, Schrijvers DM, Lion E, and Smits EL
- Subjects
- Animals, Carboxymethylcellulose Sodium pharmacology, Carboxymethylcellulose Sodium therapeutic use, Humans, Polylysine pharmacology, Polylysine therapeutic use, Adjuvants, Immunologic pharmacology, Adjuvants, Immunologic therapeutic use, Cancer Vaccines pharmacology, Cancer Vaccines therapeutic use, Carboxymethylcellulose Sodium analogs & derivatives, Poly I-C pharmacology, Poly I-C therapeutic use, Polylysine analogs & derivatives
- Abstract
Although cancer vaccination has yielded promising results in patients, the objective response rates are low. The right choice of adjuvant might improve the efficacy. Here, we review the biological rationale, as well as the preclinical and clinical results of polyinosinic:polycytidylic acid and its derivative poly-ICLC as cancer vaccine adjuvants. These synthetic immunological danger signals enhanced vaccine-induced anti-tumor immune responses and contributed to tumor elimination in animal tumor models and patients. Supported by these results, poly-ICLC-containing cancer vaccines are currently extensively studied in the ongoing trials, making it highly plausible that poly-ICLC will be part of the future approved cancer immunotherapies., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
31. HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells.
- Author
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Van den Bergh JM, Guerti K, Willemen Y, Lion E, Cools N, Goossens H, Vorsters A, Van Tendeloo VF, Anguille S, Van Damme P, and Smits EL
- Subjects
- Cells, Cultured, Dendritic Cells metabolism, Dendritic Cells pathology, Female, Humans, Immunity, Innate immunology, Immunophenotyping, Interleukin-15 immunology, Interleukin-15 metabolism, Killer Cells, Natural metabolism, Killer Cells, Natural pathology, Lymphocytes immunology, Lymphocytes metabolism, Lymphocytes pathology, Papillomavirus Infections pathology, Papillomavirus Infections prevention & control, T-Lymphocytes, Cytotoxic metabolism, T-Lymphocytes, Cytotoxic pathology, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms prevention & control, Dendritic Cells immunology, Killer Cells, Natural immunology, Papillomaviridae immunology, Papillomavirus Infections immunology, Papillomavirus Vaccines therapeutic use, T-Lymphocytes, Cytotoxic immunology, Uterine Cervical Neoplasms immunology
- Abstract
Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Published
- 2014
- Full Text
- View/download PDF
32. Interleukin-15 dendritic cells as vaccine candidates for cancer immunotherapy.
- Author
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Anguille S, Lion E, Van den Bergh J, Van Acker HH, Willemen Y, Smits EL, Van Tendeloo VF, and Berneman ZN
- Subjects
- Drug Discovery trends, Humans, Cancer Vaccines administration & dosage, Cancer Vaccines immunology, Dendritic Cells immunology, Immunotherapy methods, Interleukin-15 immunology, Neoplasms therapy
- Abstract
Owing to their professional antigen-presenting capacity and unique potential to induce tumor antigen-specific T cell immunity, dendritic cells (DCs) have attracted much interest over the past decades for therapeutic vaccination against cancer. Clinical trials have shown that the use of tumor antigen-loaded DCs in cancer patients is safe and that it has the potential to induce anti-tumor immunity which, in some cases, culminates in striking clinical responses. Unfortunately, in a considerable number of patients, DC vaccination is unable to mount effective anti-tumor immune responses and, if it does so, the resultant immunity is often insufficient to translate into tangible clinical benefit. This underscores the necessity to re-design and optimize the current procedures for DC vaccine manufacturing. A new generation of DC vaccines with improved potency has now become available for clinical use as a result of extensive pre-clinical research. One of the promising next-generation DC vaccine candidates are interleukin (IL)-15-differentiated DCs. In this commentary, we will compile the research data that have been obtained by our group and other groups with these so-called IL-15 DCs and summarize the evidence supporting the implementation of IL-15 DCs in DC-based cancer vaccination regimens.
- Published
- 2013
- Full Text
- View/download PDF
33. Dendritic cell vaccination in acute myeloid leukemia.
- Author
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Anguille S, Willemen Y, Lion E, Smits EL, and Berneman ZN
- Subjects
- Animals, Cancer Vaccines immunology, Humans, Immunotherapy, Leukemia, Myeloid, Acute therapy, Translational Research, Biomedical, Dendritic Cells immunology, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute prevention & control, Vaccination
- Abstract
The prognosis of patients with acute myeloid leukemia (AML) remains dismal, with a 5-year overall survival rate of only 5.2% for the continuously growing subgroup of AML patients older than 65 years. These patients are generally not considered eligible for intensive chemotherapy and/or allogeneic hematopoietic stem cell transplantation because of high treatment-related morbidity and mortality, emphasizing the need for novel, less toxic, treatment alternatives. It is within this context that immunotherapy has gained attention in recent years. In this review, we focus on the use of dendritic cell (DC) vaccines for immunotherapy of AML. DC are central orchestrators of the immune system, bridging innate and adaptive immunity and critical to the induction of anti-leukemic immunity. We discuss the rationale and basic principles of DC-based therapy for AML and review the clinical experience that has been obtained so far with this form of immunotherapy for patients with AML.
- Published
- 2012
- Full Text
- View/download PDF
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