- Next generation therapeutic antibodies
- Fc receptors
- Innate effectorcells
- Lung virus
Dr. Jeanette Leusen, received her PhD in 1995 at the University of Amsterdam (UvA), The Netherlands, on the topic of the NADPH oxidase of neutrophils studied at Sanquin, Amsterdam. She became a Post-doc at the University Medical Center of Utrecht, first in the Cell Biology department, later Immunology. Her entry into the Fc receptor biology/ therapeutic antibodies field began when she was awarded a prestigious fellowship from the Netherlands Scientific Organization (NWO). In the last 15 years Dr Leusen’s research has enjoyed successes promoting the notion of inside-out signaling of FcgRI as regulated by the intracellular protein periplakin (PNAS and J Biol Chem 2004). Notably, these data provided a new concept for the role of Fc receptors, which has been supported by others. I propose that all Fc receptors are under inside-out control, as we have shown for FcaR (J. Immunology 2008). Recently we have shown the physical consequences of this inside-out control for FcgRI (Blood, 2010, J. Immunol. 2011, and manuscript in preparation). At present, Dr. Leusen aims to identify the mechanism and consequences for antibody treatment of patients with antibody-based medicines that are just becoming mainstream in the Oncology clinic.
In parallel, she is actively involved in the in vivo studies of therapeutic antibodies using several mouse models. Within the immunotherapy group, a unique panel of Fc receptor knock-out and transgenic animals has been developed and obtained over the past decades (e.g. Immunity, 2001; Cancer Research 2006, J.Immunol, 2014). Supported by grants from KWF and AICR, Dr Leusen’s lab has generated and characterized a new transgenic mouse reconstituting FcR expression but incapable of ADCC. Interestingly, in both lymphoid and solid tumor models, therapy with several mAbs was completely abrogated in our ADCC-deficient model (Cancer Research, 2010, J. Immunol 2014). We expect to use this mouse for pre-clinical testing of many more novel therapeutic antibodies.
Last but not least, Dr. Leusen strongly believes in IgA as a novel class of antibody for treatment of both malignant as infectious disease. Recently we published for the first time in vivo efficacy of these antibodies (EMBO MM, 2013), but also Cancer Immunol Res 2015, MABs 2015, Cancer res 2015, and review in Mol Imm 2015.
- Next generation therapeutic antibodies
- Fc receptors
- Innate effectorcells
- Lung virus
Current External Activities
- Organizer of FASEB meeting on ImmunoReceptors in 2014 and June 2016, Snowmass, Colorado, USA
- Organizer of European Society for Clinical Investigations (ESCI): Phagocyte Workshop 2014
Senior Editor of scientific journals
- American Journal of Cancer Research
- American Journal of Blood Researc
Personal Fellowships & Awards
- 2000-2002 NWO grant (# 901-07-229) “Cell biology of FcgRI (CD64): role in antigen presentation” Now known as VENI.
- Best collaborative research project of 2007, UMCU
- Selected for the “Steyn Parvé” training and coaching program 2006 - 2008 of University of Utrecht, for excellent female senior investigators.
10 selected from 86 publications:
- Lohse S, Meyer S, Meulenbroek LA, Jansen JH, Nederend M, Kretschmer A, Klausz K, Möginger U, Derer S, Rösner T, Kellner C, Schewe D, Sondermann P, Tiwari S, Kolarich D, Peipp M, Leusen JH, Valerius T. An Anti-EGFR IgA That Displays Improved Pharmacokinetics and Myeloid Effector Cell Engagement In Vivo. Cancer Res. 2016 Jan 15;76(2):403-17. doi: 10.1158/0008-5472.CAN-15-1232. Epub 2015 Dec 3.
- Leusen JHW. IgA as therapeutic antibody. Mol Immunol. 2015 Nov;68(1):35-9. doi: 10.1016/j.molimm.2015.09.005. Review.
- Brandsma AM, Jacobino SR, Meyer S, ten Broeke T, Leusen JHW Fc receptor inside-out signaling and possible impact on antibody therapy. Immunol Rev. 2015 Nov;268(1):74-87. doi: 10.1111/imr.12332. Review.
- Meyer S, Nederend M, Jansen JH, Reiding KR, Jacobino SR, Meeldijk J, Bovenschen N, Wuhrer M, Valerius T, Ubink R, Boross P, Rouwendal G, Leusen JHW Improved in vivo anti-tumor effects of IgA-Her2 antibodies through half-life extension and serum exposure enhancement by FcRn targeting. MAbs. 2016 Jan 2;8(1):87-98. doi: 10.1080/19420862.2015.1106658. Epub 2015 Oct 14.
- Brandsma AM, Ten Broeke T, Nederend M, Meulenbroek LA, van Tetering G, Meyer S, Jansen JH, Beltrán Buitrago MA, Nagelkerke SQ, Németh I, Ubink R, Rouwendal G, Lohse S, Valerius T, Leusen JH, Boross P. Simultaneous Targeting of FcγRs and FcαRI Enhances Tumor Cell Killing. Cancer Immunol Res. 2015 Dec;3(12):1316-24. doi: 10.1158/2326-6066.CIR-15-0099-T. Epub 2015 Sep 25.
- Büll C, Boltje TJ, van Dinther EA, Peters T, de Graaf AM, Leusen JHW, Kreutz M, Figdor CG, den Brok MH, Adema GJ. Targeted Delivery of a Sialic Acid-Blocking Glycomimetic to Cancer Cells Inhibits Metastatic Spread. ACS Nano. 2015 Jan 27;9(1):733-45. doi: 10.1021/nn5061964. Epub 2015 Jan 14.
- Boross P, van Montfoort N, Stapels DA, van der Poel CE, Bertens C, Meeldijk J, Jansen JH, Verbeek JS, Ossendorp F, Wubbolts R, Leusen JHW. FcRγ-chain ITAM signaling is critically required for cross-presentation of soluble antibody-antigen complexes by dendritic cells. J Immunol. 2014 Dec 1;193(11):5506-14. doi: 10.4049/jimmunol.1302012. Epub 2014 Oct 29.
- P. Boross, S. Lohse, M. Nederend, J.H.M. Jansen, G. van Tetering, M. Dechant, M. Peipp, L. Royle, L.P. Liew, L. Boon, N. van Rooijen, W.K. Bleeker, P.W. Parren, J.G.J. van de Winkel, T. Valerius, J.H.W. Leusen. IgA EGFR antibodies mediate tumour killing in vivo. EMBO Mol Med 2013 8:1213-1226.
- P. Boross, J.H.W. Leusen. Boosting antibody therapy with complement. Blood. 2012 Jun 21;119(25):5945-7
- C.E. van der Poel, R.A. Karssemeijer, P. Boross, J.A. van der Linden, M. Blokland, J.G.J. van de Winkel, and J.H.W. Leusen. Cytokine induced immune complex binding to the high affinity IgG receptor, FcgRI, in the presence of monomeric IgG. Blood 2010 116:53
PROJECTS & GRANTS
- NKB/KWF grant 2002-2006 (# UU2002-2706) “Mechanisms of cooperation of FcaRI (CD89) and Mac-1 (CD11b/CD18) in tumor cytotoxicity; implications for immunotherapy”. co-applicant, PhD student and technician and expenses for 4 years.
- Meningitis Research Foundation project 2003-2005 (# 08/02): ‘Pathways that determine the endotoxic and adjuvant properties of meningococcal lipopolysaccharide’. co-applicant, 1 technician + consumables for 2 years.
- Association for International Cancer Research grant 2003-2006 (# 03-119): 'Antibody dependent tumour lysis by FcaRI (CD89) is regulated by Mac-1 (CD11b/CD18): dissection of signalling pathways'. Main applicant, post-doc + expenses for 3 years
- Genmab 2006-2007. “Unibody” and “Mechanisms of action of new therapeutic antibodies”, Main and only applicant (1.3 FTE)
- NWO ALW, project ALW2PJ/05088 (2006-2010) ”Effector proteins of the high affinity IgG receptor, Fc gamma RI (CD64)”. Main and only applicant, PhD student for 4 years and expenses
- Association for International Cancer Research grant (AICR) 06-368 “Mechanisms for antibody-therapeutics of cancer”. Main and only applicant, post-doc + expenses for 3 years
- Genmab, 2007-2008: “Mechanisms of action of new therapeutic antibodies; involvement of FcR ITAM”, Main and only applicant, 1 technician + animal costs + consumables
- UMCU “beleidsruimte” 2007: “Bioluminescent Imaging of Tumor Models”: Main applicant, technician one year + animal costs + consumables
- UMCU division DLA, 2008 “resistance to antibody therapy of cancer”, co-applicant, technician one year + animal costs + consumables
- Genmab, 2008-2009: “Mechanisms of action of new therapeutic antibodies; involvement of FcR ITAM” and “IgA as a therapeutic antibody”, Main and only applicant, 2 technicians + animal costs + consumables
- UMC “beleidsruimte” 2008: Zeiss LSM 710 confocal microscope, Main applicant
- Genmab, 2009-2010: “Mechanisms of action of new therapeutic antibodies; trogocytosis and involvement of FcR ITAM”, Main and only applicant, 2 technicians + animal costs + consumables
- Genmab, 2010-2011: “New immunisation method for difficult targets”, Main and only applicant, 1 technician + animal costs + consumables
- Synthon BV, 2010-2012 “Kinetics of antibodies in vivo” and “Improved therapeutic antibodies”
- IICU Seeding Grant 2011-2012, shared with Dr. R. Wubbolts, DGK UU “Fc receptor regulated antigen presentation by dendritic cells”
- AICR grant 11-012, 2011-2014 ‘IgA as new therapeutic antibody’ Main and only applicant, post-doc + expenses for 3 years
- ERC stimulation grant (UU) 2011-2015: IgA as new therapeutic antibody for viruses, PhD student for 4 years
- Synthon BV 2012-2017: next generation antibodies: 3 fte for 5 years
- Friesland-Campina 2012-2013: Immune regulation by cow’s milk: postdoc for 6 months
- Merus BV 2012-2013: ADCC capacity of novel therapeutic antibodies, postdoc and technician, ongoing
- Genmab BV 2013-2015: effect of gene polymorphisms on therapeutic antibodies (technician)
- NWO/STW 2013-2017: MIRACLE (PhD student, 4 years)
- Friesland-Campina 2014-2015: Immune regulation by cow’s milk: postdoc for 4 months
- Medimmune 2014-2015: IgA hybrids in vivo (Post-doc + technician, 1 year)
- Genmab BV 2015-2017: effect of gene polymorphisms on therapeutic antibodies (technician)
- KWF grant 2015-2020: IgA as next generation antibody for treatment of cancer (PhD student and technician for 4 years)
- KiKa grant 2016-2019: IgA isotype anti-CD20 antibodies: a novel treatment for B-cell malignancies in children and pediatric leukemia patients that suffer from B-cell diseases after stem cell transplantation (Post-doc for 3 years)
Associated Team Members
- Toine ten Broeke, Post-Doc
- Marco Jansen, technician
- Maaike Nederend, technician
- Petra Moerer, technician
- Mojtaba Amini, technician
- Saskia Meyer, PhD student
- Shamir Jacobino, PhD student
- Arianne Brandsma, PhD student
- Mitchell Evers, PhD student
- Gittan Blezer, master student BMS
- Arthur van Stigt, Medical student
- Arthur van den Burg, Honours student BMS