Next generation therapeutic antibodies
Dr. Jeanette Leusen, received her PhD in 1995 at the University of Amsterdam, The Netherlands. Her entry into the field of therapeutic antibodies and their modes of action began when she was awarded a prestigious fellowship from the Netherlands Scientific Organization (NWO). 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, J. exp. Med 2017).
Last but not least, Dr. Leusen strongly believes in IgA as a novel class of antibody for treatment of both malignant as infectious disease. In 2013 she published for the first time in vivo efficacy of IgA antibodies (EMBO MM, 2013), but more studies were published in Cancer Immunol Res 2015, MABs 2015, Cancer res 2015 and 2016, reviewed in Mol Imm 2015.
Next generation therapeutic antibodies
Neutrophils and macrophages
Current External Activities
Chair of the Gordon Research Conference on Antibody Biology and Engineering in 2018 (vice) and 2020
Co-organizer and session chair of the second European Antibody Engineering and Therapeutics meeting. Amsterdam, The Netherlands 2019
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 Research
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 107 publications:
Logtenberg MEW, Jansen JHM, Raaben M, Toebes M, Franke K, Brandsma AM, Matlung HL, Fauster A, Gomez-Eerland R, Bakker NAM, van der Schot S, Marijt KA, Verdoes M, Haanen JBAG, van den Berg JH, Neefjes J, van den Berg TK, Brummelkamp TR, Leusen JHW*, Scheeren FA*, Schumacher TN*. Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPα axis and a target for cancer immunotherapy. Nat Med. 2019 Apr;25(4):612-619. doi: 10.1038/s41591-019-0356-z. Epub 2019 Mar 4. PMID: 30833751
Brandsma AM, Schwartz SL, Wester MJ, Valley CC, Blezer GLA, Vidarsson G, Lidke KA, Ten Broeke T, Lidke DS, Leusen JHW. Mechanisms of inside-out signaling of the high-affinity IgG receptor FcγRI. Sci Signal. 2018 Jul 24;11(540). pii: eaaq0891. doi: 10.1126/scisignal.aaq0891. PMID: 30042128
Brandsma AM, Hogarth PM, Nimmerjahn F, Leusen JHW. Clarifying the Confusion between Cytokine and Fc Receptor "Common Gamma Chain". Immunity. 2016 Aug 16;45(2):225-6. doi: 10.1016/j.immuni.2016.07.006
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.
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.
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)
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)
Villa Joep! Grant 2017-2021: Improved immunotherapy for neuroblastoma (PhD student and technician for 4 years)
Argenx 2018-2021: studying new inhibitors for classical complement factor (2 Post-Docs and 2,5 technicians for 3 years)
Nutricia 2018 -2022: PRIMA project on human milk (1 PhD student, 4 years)
KWF grant 2019-2013: IgA2.0 as novel antibody therapy combined with innate checkpoint inhibition (PhD student and technician for 4 years)
Associated Team Members
Geert van Tetering, senior scientist
Kevin Budding, Post-Doc
Marco Jansen, senior technician
Maaike Nederend, technician
Petra Moerer, technician
Kim Dijkxhoorn, technician
Lauri Bloemenkamp, technician (neurology)
Elisabeth de Zeeuw, technician
Mitchell Evers, PhD student
Marjolein Stip, PhD student
Arthur van Stigt, medical PhD student (paediatrics)
Chilan Chan, PhD student
Stuart Leishman, master student BMS
Frederique van den Haak, master student BMS
Rebecca Binzberger, master student PHARM
Caroline de Jongh, master student
Corine Pleijte, honours student MED