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Ruurd Torensma

Name of the laboratory

Members of the laboratory

Head of the Unit

Ruurd Torensma r.torensma@ncmls.ru.nl

PostDoc

Bas Jansen b.jansen@ncmls.ru.nl

Ph.D. students

Refika Yigit r.yigit@obgyn.umcn.nl

Jiabo Di j.di@ncmls.ru.nl

Technician

Tjitske Duiveman-de Boer t.duiveman@ncmls.ru.nl

Laboratory activity

The department of Tumorimmunology is performing basic research on immune cells with an emphasis on dendritic cells to exploit those cells to eradicate cancer cells. We strive to translate the research findings into immune therapeutics. We have more than 10 years experience with treating melanoma patients with DC loaded with tumor antigens. We also study cord blood and bone marrow derived Mesenchymal stem cells. Recently, this has been extended to tumor initiating cells (Cancer stem cells). Also here we have an emphasis on the interaction between the tumor and the immune system. As a model we study ovarian carcinoma since it brings together oncology (cancer stem cells) and immunology. Those tumors contain also fast amounts of Treg cells, plasmacytoid DC and immune modulating cytokines. Monoclonal antibodies are raised to the cells to identify putative immunological targets and to enable the isolation of the different cell types. Monoclonal antibodies produced comprise adhesion molecules (LFA-1), stem cell antigens (CD166, CD13) and DC specific proteins (DC-SIGN and CCL18) and several antibodies that recognize so far unidentified molecules.

Research activities

Characterization of the expression and function of immune cells found in ovarian carcinoma ascites:
Our team has produced several antibodies against the immune cells found in ovarian cancer associated ascites. Characterisation of the recognized antigens in under study.

Other antibodies:
Antibodies against other molecules produced in our lab include  a neutralizing human TNF monoclonal and a monoclonal against SSX.

Production of antibodies against other cancer stem cell-surface molecules:
We are currently busy to establish so-called spheres from ascites of ovarian cancer patients. These spheres contain tumor initiating cells (cancer stem cells).  When sufficient cells are collected monoclonals to these cells will be generated.  In this way we want to identify new markers for the diagnosis and treatment of ovarian cancer.

Techniques available

• monoclonal antibody production in mice
• antibodies characterization
• multi-colour flow cytometry
• immunization with transfected cells
• cancer stem cell culture (spheres)

Publications

• Verstappen J, Katsaros C, Torensma R, Von den Hoff JW. A functional model for adult stem cells in epithelial tissues. Wound Repair Regen 2009; 17:296-305.
• van Spriel AB, Sofi M, Gartlan KH, et al. The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity. Plos Pathogens 2009; 5:e1000338.
• van den Berk LCJ, Roelofs H, Huijs T, Siebers-Vermeulen KGC, Raymakers RA, Kögler G, Figdor CG, Torensma R. Cord blood mesenchymal stem cells  propel human dendritic cells to an intermediate maturation state and boost IL-12 production by mature DC. Immunol 2009; in press.
• van den Berk LCJ, Jansen BJH, Siebers-Vermeulen KGC, et al. Toll-like receptor triggering in cord blood mesenchymal stem cells. J Cell Mol Med 2009; in press.
• van den Berk LCJ, Figdor CG, Torensma R. Mesenchymal Stromal Cells: tissue engineers and immune response modulators. Archiv Immunol Ther Exp 2008; 56:1-5.
• Tacken P, Joosten B, Reddy A, et al. No advantage of cell penetrating peptides over receptor-specific antibodies in targeting antigen to human dendritic cells for cross-presentation. J Immunol 2008; 180:7687-96.
• Gijzen K, Raymakers RA, Broers KM, Figdor CG, Torensma R. Interaction of acute lymphopblastic leukemia cells with C-type lectins DC-SIGN and L-SIGN. Exp Hematol 2008; 36:860-70.
• den Dekker E, Grefte S, Huijs T, et al. Monocyte Cell Surface Glycosaminoglycans Positively Modulate IL-4-Induced Differentiation toward Dendritic Cells. J Immunol 2008; 180:3680-8.
• Torensma R, Brouwer RHJ, van Ginkel K, Figdor CG, Singh SK. Total reendothelialization of vascular grafts by circulating recipient endothelial stem cells in a transgenic green rat. Res J Med Sci 2007; 1:234-41.
• te Riet J, Zimmerman AW, Joosten B, et al. Distinct kinetic and mechanical properties govern ALCAM-mediated interactions as shown by single-molecule force spectroscopy. J Cell Sci 2007; 120:3965-76.
• Tacken P, de Vries IJ, Torensma R, Figdor CG. Dendritic cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol 2007; 7:790-802.
• Pereira CF, Torensma R, Hebeda K, Kretz-Rommel A, Faas SJ, Figdor CG, Adema GJ. In vivo targeting of DC-SIGN-positive antigen presenting cells in a nonhuman primate model. J Immunother 2007; 30:705-14.
• Kretz-Rommel A, Qin F, Dakappagari N, Torensma R, Faas S, Wu D, Bowdish K. In Vivo Targeting of Antigens to Human Dendritic Cells Through DC-SIGN Elicits Stimulatory Immune Responses and Inhibits Tumor Growth in Grafted Mouse Models J Immunother 2007; 30:715-27.
• Grefte S, Kuijpers-Jagtman AM, Torensma R, Von den Hoff JW. Skeletal muscle development and regeneration. Stem Cell Devel 2007; 16:857-68.
• Gijzen K, Tacken PJ, Zimmerman A, Joosten B, de Vries IJ, Figdor CG, Torensma R. Relevance of DC-SIGN in DC-induced T cell proliferation. J Leukoc Biol 2007; 81:729-40.
• Gijzen K, Broers KM, Beeren IM, Figdor CG, Torensma R. Binding of the adhesion and pathogen receptor DC-SIGN by monocytes is regulated by the density of Lewis X molecules. Mol Immunol 2007; 44:2481-6.
• Bladergroen BA, den Dekker E, Vermeulen KGC, Netelenbos T, Drager AM, Hebeda KM, Figdor CG, Torensma R. Spatially separated distribution and highly flexible expression of adhesion molecules facilitates dynamic hematopoiesis. J  Med Sciences 2007; 7:1239-49.
• Zimmerman AW, Joosten B, Torensma R, Parnes JR, van Leeuwen FN, Figdor CG. Long-term engagement of CD6 and ALCAM is essential for T-cell proliferation induced by dendritic cells. Blood 2006; 107:3212-20.
• Tacken PJ, Torensma R, Figdor CG. Targeting antigens to dendritic cells in vivo. Immunobiol 2006; 211:599-608.
• Netea MG, Gow NA, Munro CA, et al. Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J Clin Invest 2006; 116:1642-50.
• Dakappagari N, Maruyama T, Renshaw M, et al. Internalizing antibodies to the C-type lectins, L-SIGN and DC-SIGN, inhibit viral glycoprotein binding and deliver antigen to human dendritic cells for the induction of T cell responses. J Immunol 2006; 176:426-40.
• van der Voort R, Kramer M, Lindhout E, et al. Novel monoclonal antibodies detect elevated levels of the chemokine CCL18/DC-CK1 in serum and body fluids in pathological conditions. J Leukoc Biol 2005; 77:739-47.
• Torensma R. Blood vessels engineered from human cells. Lancet 2005; 366:892.
• Buckley CD, Halder S, Hardie D, Reynolds G, Torensma R, De Villeroche VJ, Brouty-Boye D, Isacke CM. Report on antibodies submitted to the stromal cell section of HLDA8. Cell Immunol 2005; 236:29-41.
• Torensma R, Figdor CG. Differentiating stem cells mask their origins. Stem Cells 2004; 22:250-2.
• van Lent PL, Figdor CG, Barrera P, van Ginkel K, Sloetjes A, van den Berg WB, Torensma R. Expression of the dendritic cell-associated C-type lectin DC-SIGN by inflammatory matrix metalloproteinase-producing macrophages in rheumatoid arthritis synovium and interaction with intercellular adhesion molecule 3-positive T cells. Arthritis Rheum 2003; 48:360-9.
• Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y, Figdor CG. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 2000; 100:575-85.
• Geijtenbeek TB, Kwon DS, Torensma R, et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 2000; 100:587-97.
• dos Santos NR, Torensma R, de Vries TJ, et al. Heterogeneous expression of the SSX cancer/testis antigens in human melanoma lesions and cell lines. Cancer Res 2000; 60:1654-62.
• Torensma R, Raymakers RA, van Kooyk Y, Figdor CG. Induction of LFA-1 on pluripotent CD34+ bone marrow cells does not affect lineage commitment. Blood 1996; 87:4120-8.