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631 results on '"de Gruijl, Tanja D."'

151. Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes.

Author

Affandi, Alsya J., Grabowska, Joanna, Olesek, Katarzyna, Venegas, Miguel Lopez, Barbaria, Arnaud, Ernesto Rodríguez, Mulder, Patrick P. G., Pijffers, Helen J., Ambrosini, Martino, Kalay, Hakan, O'Toole, Tom, Zwart, Eline S., Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J., Stöckl, Johannes, van den Eertwegh, Alfons J. M., de Gruijl, Tanja D., Storm, Gert, and van Kooyk, Yvette

Subjects
TUMOR antigens, CANCER vaccines, ANTIGEN receptors, T cells, DENDRITIC cells
Abstract

Priming of CD8+ T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1+ antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14+ CD169+ monocytes and Axl+ CD169+ DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169+ moDCs and Axl+ CD169+ DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8+ T cells. Finally, Axl+ CD169+ DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169+ DCs to drive antitumor T cell responses. [ABSTRACT FROM AUTHOR]

Published
2020
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152. Correction: Prevention of Vγ9Vδ2 T Cell Activation by a Vγ9Vδ2 TCR Nanobody

Author

de Bruin, Renée C G, Stam, Anita G M, Vangone, Anna, van Bergen En Henegouwen, Paul M P, Verheul, Henk M W, Sebestyén, Zsolt, Kuball, Jürgen, Bonvin, Alexandre M J J, de Gruijl, Tanja D, van der Vliet, Hans J, Sub Biomolecular Imaging, Sub NMR Spectroscopy, Sub Cell Biology, and NMR Spectroscopy

Subjects
Taverne
Published
2017

153. Generation and characterization of CD1d-specific single-domain antibodies with distinct functional features

Author

Lameris, Roeland, de Bruin, Renée C G, van Bergen en Henegouwen, Paul M P, Verheul, Henk M., Zweegman, Sonja, de Gruijl, Tanja D., van der Vliet, Hans J., Celbiologie, Sub Cell Biology, Medical oncology, CCA - Cancer immunology, AII - Cancer immunology, Medical oncology laboratory, Hematology, Celbiologie, and Sub Cell Biology

Subjects
0301 basic medicine, Phage display, Apoptosis, 0302 clinical medicine, variable domain of heavy-chain-only antibody, Taverne, Immunology and Allergy, Antigen Presentation, B-Lymphocytes, biology, Immunogenicity, Antibodies, Monoclonal, Cell Differentiation, hemic and immune systems, CD1D, lipids (amino acids, peptides, and proteins), Immunotherapy, Antibody, Clone (B-cell biology), Multiple Myeloma, Camelids, New World, invariant natural killer T-cell, medicine.drug_class, dendritic cell, Immunology, chemical and pharmacologic phenomena, Monoclonal antibody, CD1d, Cell Line, 03 medical and health sciences, Peptide Library, parasitic diseases, medicine, biology.domesticated_animal, Animals, Humans, cancer, Dendritic cell, Dendritic Cells, Original Articles, Single-Domain Antibodies, Molecular biology, Lama glama, carbohydrates (lipids), 030104 developmental biology, biology.protein, Natural Killer T-Cells, Antigens, CD1d, 030215 immunology, Single-Chain Antibodies
Abstract

Ligation of the CD1d antigen-presenting molecule by monoclonal antibodies (mAbs) can trigger important biological functions. For therapeutic purposes camelid-derived variable domain of heavy-chain-only antibodies (VHH) have multiple advantages over mAbs because they are small, stable and have low immunogenicity. Here, we generated 21 human CD1d-specific VHH by immunizing Lama glama and subsequent phage display. Two clones induced maturation of dendritic cells, one clone induced early apoptosis in CD1d-expressing B lymphoblasts and multiple myeloma cells, and another clone blocked recognition of glycolipid-loaded CD1d by CD1d-restricted invariant natural killer T (iNKT) cells. In contrast to reported CD1d-specific mAbs, these CD1d-specific VHH have the unique characteristic that they induce specific and well-defined biological effects. This feature, combined with the above-indicated general advantages of VHH, make the CD1d-specific VHH generated here unique and useful tools to exploit both CD1d ligation as well as disruption of CD1d-iNKT interactions in the treatment of cancer or inflammatory disorders.

Published
2016

154. In the mix: the potential benefits of adding GM-CSF to CpG-B in the local treatment of patients with early-stage melanoma.

Author

Koster, Bas D., de Jong, Tamarah D., van den Hout, Mari F. C. M., Sluijter, Berbel J. R., Vuylsteke, Ronald J. C. L. M., Molenkamp, Barbara G., Vosslamber, Saskia, van den Tol, M. Petrousjka, van den Eertwegh, Alfons J. M., and de Gruijl, Tanja D.

Subjects
MELANOMA, IMMUNOREGULATION, SENTINEL lymph nodes
Abstract

Whereas TLR9 agonists are recognized as powerful stimulators of antitumor immunity, GM-CSF has had mixed reviews. In previously reported randomized trials we assessed the effects of local immune modulation in early-stage melanoma with CpG-B alone or with GM-CSF. Here we discuss the added value of GM-CSF and show sex-related differences. [ABSTRACT FROM AUTHOR]

Published
2020
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155. Human Bone Marrow-Derived Myeloid Dendritic Cells Show an Immature Transcriptional and Functional Profile Compared to Their Peripheral Blood Counterparts and Separate from Slan+ Non-Classical Monocytes

Author

van Leeuwen-Kerkhoff, Nathalie, primary, Lundberg, Kristina, additional, Westers, Theresia M., additional, Kordasti, Shahram, additional, Bontkes, Hetty J., additional, Lindstedt, Malin, additional, de Gruijl, Tanja D., additional, and van de Loosdrecht, Arjan A., additional

Published
2018
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156. Indoleamine 2,3-Dioxygenase Expression Pattern in the Tumor Microenvironment Predicts Clinical Outcome in Early Stage Cervical Cancer

Author

Heeren, A. Marijne, primary, van Dijk, Ilse, additional, Berry, Daniella R. A. I., additional, Khelil, Maryam, additional, Ferns, Debbie, additional, Kole, Jeroen, additional, Musters, René J. P., additional, Thijssen, Victor L., additional, Mom, Constantijne H., additional, Kenter, Gemma G., additional, Bleeker, Maaike C. G., additional, de Gruijl, Tanja D., additional, and Jordanova, Ekaterina S., additional

Published
2018
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158. Melanoma Sequentially Suppresses Different DC Subsets in the Sentinel Lymph Node, Affecting Disease Spread and Recurrence

Author

van den Hout, Mari F.C.M., primary, Koster, Bas D., additional, Sluijter, Berbel J.R., additional, Molenkamp, Barbara G., additional, van de Ven, Rieneke, additional, van den Eertwegh, Alfons J.M., additional, Scheper, Rik J., additional, van Leeuwen, Paul A.M., additional, van den Tol, M. Petrousjka, additional, and de Gruijl, Tanja D., additional

Published
2017
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159. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells

Author

de Bruin, Renée C. G., primary, Veluchamy, John P., additional, Lougheed, Sinéad M., additional, Schneiders, Famke L., additional, Lopez-Lastra, Silvia, additional, Lameris, Roeland, additional, Stam, Anita G., additional, Sebestyen, Zsolt, additional, Kuball, Jürgen, additional, Molthoff, Carla F. M., additional, Hooijberg, Erik, additional, Roovers, Rob C., additional, Santo, James P. Di, additional, van Bergen en Henegouwen, Paul M. P., additional, Verheul, Henk M. W., additional, de Gruijl, Tanja D., additional, and van der Vliet, Hans J., additional

Published
2017
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161. Local Adjuvant Treatment with Low-Dose CpG-B Offers Durable Protection against Disease Recurrence in Clinical Stage I–II Melanoma: Data from Two Randomized Phase II Trials

Author

Koster, Bas D., primary, van den Hout, Mari F.C.M., additional, Sluijter, Berbel J.R., additional, Molenkamp, Barbara G., additional, Vuylsteke, Ronald J.C.L.M., additional, Baars, Arnold, additional, van Leeuwen, Paul A.M., additional, Scheper, Rik J., additional, Petrousjka van den Tol, M., additional, van den Eertwegh, Alfons J.M., additional, and de Gruijl, Tanja D., additional

Published
2017
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164. Highly specific and potently activating V gamma 9V delta 2-T cell specific nanobodies for diagnostic and therapeutic applications

Author

de Bruin, Renée C G, Lougheed, Sinéad M., van der Kruk, Liza, Stam, Anita G., Hooijberg, Erik, Roovers, Rob C., van Bergen en Henegouwen, Paul M P, Verheul, Henk M W, de Gruijl, Tanja D., van der Vliet, Hans J., Celbiologie, Sub Cell Biology, CCA - Cancer immunology, Medical oncology laboratory, AII - Cancer immunology, Medical oncology, Pathology, Celbiologie, and Sub Cell Biology

Subjects
0301 basic medicine, Adoptive cell transfer, T-Lymphocytes, medicine.medical_treatment, T cell, Immunology, Antibody Affinity, VHH, Biology, Gamma delta T cells, Jurkat cells, Jurkat Cells, 03 medical and health sciences, Immune system, Cancer immunotherapy, Antibody Specificity, medicine, Animals, Humans, Immunology and Allergy, Flow cytometry, Cells, Cultured, Cancer, Bispecific monoclonal antibody, Immunomagnetic Separation, Single-domain antibody fragment, Reproducibility of Results, Receptors, Antigen, T-Cell, gamma-delta, Immunotherapy, Single-Domain Antibodies, Immunohistochemistry, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Microscopy, Fluorescence, biology.protein, Nanobody, MACS, Antibody, Camelids, New World, Immunocytochemistry
Abstract

Vγ9Vδ2-T cells constitute the predominant subset of γδ-T cells in human peripheral blood and have been shown to play an important role in antimicrobial and antitumor immune responses. Several efforts have been initiated to exploit these cells for cancer immunotherapy, e.g. by using phosphoantigens, adoptive cell transfer, and by a bispecific monoclonal antibody based approach. Here, we report the generation of a novel set of Vγ9Vδ2-T cell specific VHH (or nanobody). VHH have several advantages compared to conventional antibodies related to their small size, stability, ease of generating multispecific molecules and low immunogenicity. With high specificity and affinity, the anti-Vγ9Vδ2-T cell receptor VHHs are shown to be useful for FACS, MACS and immunocytochemistry. In addition, some VHH were found to specifically activate Vγ9Vδ2-T cells. Besides being of possible immunotherapeutic value, these single domain antibodies will be of great value in the further study of this important immune effector cell subset.

Published
2016

166. Blocking Tumor-Educated MSC Paracrine Activity Halts Osteosarcoma Progression

Author

Baglio, S. Rubina, primary, Lagerweij, Tonny, additional, Pérez-Lanzón, Maria, additional, Ho, Xuan Dung, additional, Léveillé, Nicolas, additional, Melo, Sonia A., additional, Cleton-Jansen, Anne-Marie, additional, Jordanova, Ekaterina S., additional, Roncuzzi, Laura, additional, Greco, Michelina, additional, van Eijndhoven, Monique A.J., additional, Grisendi, Giulia, additional, Dominici, Massimo, additional, Bonafede, Roberta, additional, Lougheed, Sinead M., additional, de Gruijl, Tanja D., additional, Zini, Nicoletta, additional, Cervo, Silvia, additional, Steffan, Agostino, additional, Canzonieri, Vincenzo, additional, Martson, Aare, additional, Maasalu, Katre, additional, Köks, Sulev, additional, Wurdinger, Tom, additional, Baldini, Nicola, additional, and Pegtel, D. Michiel, additional

Published
2017
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171. Ablation of Locally Advanced Pancreatic Cancer with Percutaneous Irreversible Electroporation: Results of the Phase I/II PANFIRE Study

Author

Scheffer, Hester J., primary, Vroomen, Laurien G. P. H., additional, de Jong, Marcus C., additional, Melenhorst, Marleen C. A. M., additional, Zonderhuis, Babs M., additional, Daams, Freek, additional, Vogel, Jantien A., additional, Besselink, Marc G. H., additional, van Kuijk, Cornelis, additional, Witvliet, Jill, additional, de van der Schueren, Marian A. E., additional, de Gruijl, Tanja D., additional, Stam, Anita G. M., additional, van den Tol, Petrousjka M. P., additional, van Delft, Foke, additional, Kazemier, Geert, additional, and Meijerink, Martijn R., additional

Published
2017
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174. High-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of HLA status

Author

Veluchamy, John P., primary, Heeren, A. Marijne, additional, Spanholtz, Jan, additional, van Eendenburg, Jaap D. H., additional, Heideman, Daniëlle A. M., additional, Kenter, Gemma G., additional, Verheul, Henk M., additional, van der Vliet, Hans J., additional, Jordanova, Ekaterina S., additional, and de Gruijl, Tanja D., additional

Published
2016
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175. Immune-competent human skin disease models

Author

Bergers, Lambert I.J.C., primary, Reijnders, Christianne M.A., additional, van den Broek, Lenie J., additional, Spiekstra, Sander W., additional, de Gruijl, Tanja D., additional, Weijers, Ester M., additional, and Gibbs, Susan, additional

Published
2016
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176. Autologous tumor cell vaccination combined with systemic CpG-B and IFN-α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial.

Author

Koster, Bas D., Santegoets, Saskia J. A. M., Harting, Jorien, Baars, Arnold, van Ham, S. Marieke, Scheper, Rik J., Hooijberg, Erik, de Gruijl, Tanja D., and van den Eertwegh, Alfons J. M.

Subjects
BCG vaccines, HEPATITIS B vaccines, CANCER vaccines, RENAL cell carcinoma, HEPATITIS associated antigen
Published
2019
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177. Metronomic cyclophosphamide attenuates mTOR-mediated expansion of regulatory T cells, but does not impact clinical outcome in patients with metastatic renal cell cancer treated with everolimus.

Author

Werter, Inge M., Huijts, Charlotte M., Lougheed, Sinéad. M., Hamberg, Paul, Polee, Marco B., Tascilar, Metin, Los, Maartje, Haanen, John B. A. G., Helgason, Helgi H., Verheul, Henk M., de Gruijl, Tanja D., and van der Vliet, Hans J.

Subjects
EVEROLIMUS, RENAL cancer, T cells, VASCULAR endothelial growth factors, CANCER cells
Abstract

Introduction: Metastatic renal cell cancer (mRCC) patients have a median overall survival (mOS) of approximately 28 months. Until recently, mammalian target of rapamycin (mTOR) inhibition with everolimus was the standard second-line treatment regimen for mRCC patients, improving median progression-free survival (mPFS). Treatment with everolimus supports the expansion of immunosuppressive regulatory T cells (Tregs), which exert a negative effect on antitumor immune responses. In a phase 1 dose-escalation study, we have recently demonstrated that a low dose of 50 mg oral cyclophosphamide once daily can be safely combined with everolimus in mRCC patients and prevents the everolimus-induced increase in Tregs. Materials and methods: In a multicenter phase 2 study, performed in patients with mRCC not amenable to or progressive on a vascular endothelial growth factor (VEGF)-receptor tyrosine kinase inhibitor (TKI) containing treatment regimen, we assessed whether the addition of this metronomic dosing schedule of cyclophosphamide to therapy with everolimus could result in an improvement of progression-free survival (PFS) after 4 months of treatment. Results: Though results from this study confirmed that combination treatment effectively lowered circulating levels of Tregs, addition of cyclophosphamide did not improve the PFS rate at 4 months. For this reason, the study was abrogated at the predefined interim analysis. Conclusion: Although the comprehensive immunomonitoring analysis performed in this study provides relevant information for the design of future immunotherapeutic approaches, the addition of metronomic cyclophosphamide to mRCC patients receiving everolimus cannot be recommended. [ABSTRACT FROM AUTHOR]

Published
2019
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178. The effect of everolimus and low-dose cyclophosphamide on immune cell subsets in patients with metastatic renal cell carcinoma: results from a phase I clinical trial.

Author

Huijts, Charlotte M., Lougheed, Sinéad M., Bodalal, Zuhir, van Herpen, Carla M., Hamberg, Paul, Tascilar, Metin, Haanen, John B., Verheul, Henk M., de Gruijl, Tanja D., van der Vliet, Hans J., and for the Dutch WIN-O Consortium

Subjects
EVEROLIMUS, RENAL cell carcinoma, CLINICAL trials, RENAL cancer, T cells, MTOR inhibitors
Abstract

For the treatment of metastatic renal cell cancer several strategies are used among which the mTOR inhibitor everolimus. As mTOR plays an important role in the immune system, e.g., by controlling the expression of the transcription factor FoxP3 thereby regulating regulatory T cells (Tregs), it plays a key role in the balance between tolerance and inflammation. Previous reports showed stimulatory effects of mTOR inhibition on the expansion of Tregs, an effect that can be considered detrimental in terms of cancer control. Since metronomic cyclophosphamide (CTX) was shown to selectively deplete Tregs, a phase 1 clinical trial was conducted to comprehensively investigate the immune-modulating effects of several dosages and schedules of CTX in combination with the standard dose of everolimus, with the explicit aim to achieve selective Treg depletion. Our data show that 50 mg of CTX once daily and continuously administered, in combination with the standard dose of 10 mg everolimus once daily, not only results in depletion of Tregs, but also leads to a reduction in MDSC, a sustained level of the CD8+ T-cell population accompanied by an increased effector to suppressor ratio, and reversal of negative effects on three peripheral blood DC subsets. These positive effects on the immune response may contribute to improved survival, and therefore this combination therapy is further evaluated in a phase II clinical trial. [ABSTRACT FROM AUTHOR]

Published
2019
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179. Phase 1 study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell carcinoma.

Author

Huijts, Charlotte M., Werter, Inge M., Lougheed, Sinéad M., Goedegebuure, Ruben S., van Herpen, Carla M., Hamberg, Paul, Tascilar, Metin, Haanen, John B., Verheul, Henk M., de Gruijl, Tanja D., van der Vliet, Hans J., and for the Dutch WIN-O Consortium

Subjects
CYCLOPHOSPHAMIDE, MTOR inhibitors, RENAL cell carcinoma, RENAL cancer
Abstract

Abstract: mTOR inhibitors are frequently used in the treatment of metastatic renal cell cancer (mRCC). mTOR regulates cell growth, proliferation, angiogenesis, and survival, and additionally plays an important role in immune regulation. Since mTOR inhibitors were shown to benefit immunosuppressive regulatory T-cell (Treg) expansion, this might suppress antitumor immune responses. Metronomic cyclophosphamide (CTX) was shown to selectively deplete Tregs. This study was, therefore, designed to determine the optimal dosage and schedule of CTX when combined with everolimus to prevent this potentially detrimental Treg expansion. In this national multi-center phase I study, patients with mRCC progressive on first line anti-angiogenic therapy received 10 mg everolimus once daily and were enrolled into cohorts with different CTX dosages and schedules. Besides immune monitoring, adverse events and survival data were monitored. 40 patients, 39 evaluable, were treated with different doses and schedules of CTX. Combined with 10 mg everolimus once daily, the optimal Treg depleting dose and schedule of CTX was 50 mg CTX once daily. 23 (59%) patients experienced one or more treatment-related ≥ grade 3 toxicity, mostly fatigue, laboratory abnormalities and pneumonitis. The majority of the patients achieved stable disease, two patients a partial response. Median PFS of all cohorts was 3.5 months. In conclusion, the optimal Treg depleting dose and schedule of CTX, when combined with everolimus, is 50 mg once daily. This combination leads to acceptable adverse events in comparison with everolimus alone. Currently, the here selected combination is being evaluated in a phase II clinical trial.Trial registration: NCT01462214. [ABSTRACT FROM AUTHOR]

Published
2019
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180. A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia.

Author

van de Loosdrecht, Arjan A., van Wetering, Sandra, Santegoets, Saskia J. A. M., Singh, Satwinder Kaur, Eeltink, Corien M., den Hartog, Yvonne, Koppes, Malika, Kaspers, Jorn, Ossenkoppele, Gert J., Kruisbeek, Ada M., and de Gruijl, Tanja D.

Subjects
ACUTE myeloid leukemia, T cells, CANCER chemotherapy, ANTINEOPLASTIC combined chemotherapy protocols, MYELOID leukemia
Abstract

In elderly acute myeloid leukemia (AML) patients post-remission treatment options are associated with high comorbidity rates and poor survival. Dendritic cell (DC)-based immunotherapy is a promising alternative treatment strategy. A novel allogeneic DC vaccine, DCP-001, was developed from an AML-derived cell line that uniquely combines the positive features of allogeneic DC vaccines and expression of multi-leukemia-associated antigens. Here, we present data from a phase I study conducted with DCP-001 in 12 advanced-stage elderly AML patients. Patients enrolled were in complete remission (CR1/CR2) (n = 5) or had smoldering disease (n = 7). All patients were at high risk of relapse and ineligible for post-remission intensification therapies. A standard 3 + 3 dose escalation design with extension to six patients in the highest dose was performed. Patients received four biweekly intradermal DCP-001 injections at different dose levels (10, 25, and 50 million cells DCP-001) and were monitored for clinical and immunological responses. Primary objectives of the study (feasibility and safety) were achieved with 10/12 patients completing the vaccination program. Treatment was well tolerated. A clear-cut distinction between patients with and without detectable circulating leukemic blasts during the vaccination period was noted. Patients with no circulating blasts showed an unusually prolonged survival [median overall survival 36 months (range 7-63) from the start of vaccination] whereas patients with circulating blasts, died within 6 months. Long-term survival was correlated with maintained T cell levels and induction of multi-functional immune responses. It is concluded that DCP-001 in elderly AML patients is safe, feasible and generates both cellular and humoral immune responses. [ABSTRACT FROM AUTHOR]

Published
2018
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182. TLR2 ligand-synthetic long peptide conjugates effectively stimulate tumor-draining lymph node T cells of cervical cancer patients

Author

Zom, Gijs G., primary, Welters, Marij J.P., additional, Loof, Nikki M., additional, Goedemans, Renske, additional, Lougheed, Sinéad, additional, Valentijn, Rob R.P.M., additional, Zandvliet, Maarten L., additional, Meeuwenoord, Nico J., additional, Melief, Cornelis J.M., additional, de Gruijl, Tanja D., additional, Van der Marel, Gijsbert A., additional, Filippov, Dmitri V., additional, Ossendorp, Ferry, additional, and Van der Burg, Sjoerd H., additional

Published
2016
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183. High myeloid‐derived suppressor cell frequencies in the duodenum are associated with enteropathy associated T‐cell lymphoma and its precursor lesions

Author

Bontkes, Hetty J., primary, Jordanova, Ekaterina S., additional, Nijeboer, Petula, additional, Neefjes‐Borst, Eskelina A., additional, Cillessen, Saskia A.G.M., additional, Hayat, Amjad, additional, Mulder, Chris J., additional, Bouma, Gerd, additional, von Blomberg, Boudewina M., additional, and de Gruijl, Tanja D., additional

Published
2016
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185. Allogeneic NK cells generated from cord blood as universal treatment for cervical cancer enabled by HLA independent killing mechanisms.

Author

Veluchamy, John, primary, Heeren, A.Marijne, additional, Spanholtz, Jan, additional, van Eendenburg, Jaap D.H, additional, Heideman, Danielle, additional, Verheul, Henk M.W., additional, Kenter, Gemma, additional, Van Der Vliet, Hans J., additional, Jordanova, Ekaterina S., additional, and de Gruijl, Tanja D., additional

Published
2016
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187. Apoptotic vesicles as tumor vaccine

Author

Horrevorts, Sophie K, primary, Garcia-Vallejo, Juan J, additional, van Vliet, Sandra J, additional, van de Loosdrecht, Arjan A, additional, van Kooyk, Yvette, additional, and de Gruijl, Tanja D, additional

Published
2016
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188. Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells

Author

van Dodewaard-de Jong, Joyce M., primary, Santegoets, Saskia JAM, additional, van de Ven, Peter M., additional, Versluis, Jurjen, additional, Verheul, Henk M. W., additional, de Gruijl, Tanja D., additional, Gerritsen, Winald R., additional, and van den Eertwegh, Alfons J. M., additional

Published
2015
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190. Chronic Lymphocytic Leukemia (CLL) Cells Are Susceptible to γδ-T Cell Mediated Killing, Provided CLL-Derived γδ-T Cell Dysfunction Can be Reversed

Author

de Weerdt, Iris, primary, Terpstra, Sanne, additional, Hofland, Tom, additional, Lameris, Roeland, additional, de Bruin, Renee C.G., additional, Levin, Mark-David, additional, Remmerswaal, Ester B.M., additional, ten Berge, Ineke J.M., additional, Tonino, Sanne H., additional, de Gruijl, Tanja D, additional, van der Vliet, Hans, additional, and Kater, Arnon P., additional

Published
2015
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193. Adjuvant treatment of early-stage melanoma by local i.d. administration of low-dose CpG-B and GM-CSF increases recurrence-free survival: long-term follow-up of three randomized clinical trials

Author

de Gruijl, Tanja D, primary, Koster, Bas D, additional, van den Hout, Mari FCM, additional, Sluijter, Berbel JR, additional, Molenkamp, Barbara G, additional, Vuylsteke, Ronald JCLM, additional, van Leeuwen, Paul AM, additional, Scheper, Rik J, additional, van den Tol, Petrousjka, additional, and van den Eertwegh, Alfons, additional

Published
2015
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194. Counteracting breast-cancer induced immune suppression by reactivating lymph node-resident conventional dendritic cells (LNR-cDC)

Author

van de Ven, Rieneke, primary, van Pul, Kim, additional, Aliabadi, Shaghayegh, additional, van den Tol, Petrousjka, additional, te Velde, Lisette A, additional, Rutgers, Emiel JTh, additional, Vuylsteke, Ronald JCLM, additional, Stockmann, Hein BAC, additional, Dubay, Christopher, additional, Harrington, Chris, additional, Fox, Bernard A, additional, and de Gruijl, Tanja D, additional

Published
2015
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196. Multifactorial resistance to aminopeptidase inhibitor prodrug CHR2863 in myeloid leukemia cells: down-regulation of carboxylesterase 1, drug sequestration in lipid droplets and pro-survival activation ERK/Akt/mTOR

Author

Verbrugge, Sue Ellen, primary, Al, Marjon, additional, Assaraf, Yehuda G., additional, Kammerer, Sarah, additional, Chandrupatla, Durga M.S.H., additional, Honeywell, Richard, additional, Musters, Rene P.J., additional, Giovannetti, Elisa, additional, O’Toole, Tom, additional, Scheffer, George L., additional, Krige, David, additional, de Gruijl, Tanja D., additional, Niessen, Hans W.M., additional, Lems, Willem F., additional, Kramer, Pieternella A., additional, Scheper, Rik J., additional, Cloos, Jacqueline, additional, Ossenkoppele, Gert J., additional, Peters, Godefridus J., additional, and Jansen, Gerrit, additional

Published
2015
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197. Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells

Author

Fehres, Cynthia M, primary, Duinkerken, Sanne, additional, Bruijns, Sven CM, additional, Kalay, Hakan, additional, van Vliet, Sandra J, additional, Ambrosini, Martino, additional, de Gruijl, Tanja D, additional, Unger, Wendy WJ, additional, Garcia-Vallejo, Juan J, additional, and van Kooyk, Yvette, additional

Published
2015
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200. Improving CLL Vγ9Vδ2-T–cell fitness for cellular therapy by ex vivo activation and ibrutinib

Author

de Weerdt, Iris, Hofland, Tom, Lameris, Roeland, Endstra, Sanne, Jongejan, Aldo, Moerland, Perry D., de Bruin, Renee C.G., Remmerswaal, Ester B.M., ten Berge, Ineke J.M., Liu, Nora, van der Stelt, Mario, Faber, Laura M., Levin, Mark-David, Eldering, Eric, Tonino, Sanne H., de Gruijl, Tanja D., van der Vliet, Hans J., and Kater, Arnon P.

Abstract

The efficacy of autologous (αβ) T-cell–based treatment strategies in chronic lymphocytic leukemia (CLL) has been modest. The Vγ9Vδ2-T cell subset consists of cytotoxic T lymphocytes with potent antilymphoma activity via a major histocompatibility complex–independent mechanism. We studied whether Vγ9Vδ2-T cells can be exploited as autologous effector lymphocytes in CLL. Healthy control Vγ9Vδ2-T cells were activated by and had potent cytolytic activity against CLL cells. However, CLL-derived Vγ9Vδ2-T cells proved dysfunctional with respect to effector cytokine production and degranulation, despite an increased frequency of the effector-type subset. Consequently, cytotoxicity against malignant B cells was hampered. A comparable dysfunctional phenotype was observed in healthy Vγ9Vδ2-T cells after coculture with CLL cells, indicating a leukemia-induced mechanism. Gene-expression profiling implicated alterations in synapse formation as a conceivable contributor to compromised Vγ9Vδ2-T–cell function in CLL patients. Dysfunction of Vγ9Vδ2-T cells was fully reversible upon activation with autologous monocyte-derived dendritic cells (moDCs). moDC activation resulted in efficient expansion and predominantly yielded Vγ9Vδ2-T cells with a memory phenotype. Furthermore, ibrutinib treatment promoted an antitumor T helper 1 (TH1) phenotype in Vγ9Vδ2-T cells, and we demonstrated binding of ibrutinib to IL-2-inducible kinase (ITK) in Vγ9Vδ2-T cells. Taken together, CLL-mediated dysfunction of autologous Vγ9Vδ2-T cells is fully reversible, resulting in potent cytotoxicity toward CLL cells. Our data support the potential use of Vγ9Vδ2-T cells as effector T cells in CLL immunotherapy and favor further exploration of combining Vγ9Vδ2-T-cell–based therapy with ibrutinib.

Published
2018
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