Paul Parren
Professor Molecular Immunology
- Name
- Prof.dr. P.W.H.I. Parren
- Telephone
- +31 71 526 9111
- p.w.h.i.parren@lumc.nl
Paul W.H.I. Parren is professor of Molecular Immunology at the Leiden University Medical Center (LUMC). He is Executive Vice President and head of Research and Development at LAVA Therapeutics, a Nasdaq-listed biotechnology company in Utrecht and Philadelphia, PA. He advises start-up biotechnology companies and pharma on therapeutic antibody development and patents. He is an Operational Partner at Gilde Healthcare in Utrecht. He is also a member of the Board of Directors of the non-profit organization The Antibody Society and a member of the Scientific Advisory Boards of the annual Antibody Engineering and Therapeutics conferences in US and EU, Keystone Symposia on Molecular and Cellular Biology, and the Viral Immunotherapeutic Consortium, a US NIH-funded international consortium to discover and deliver antibody therapeutics against multiple families of emerging infectious diseases. He is a member of the External Advisory Group for the Scientific Research Partnership for Neglected Tropical Snakebite (SRPNTS) program sponsored by the UK Department for International Development.
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Paul W.H.I. Parren is professor of Molecular Immunology at the Leiden University Medical Center (LUMC). He is Executive Vice President and head of Research and Development at LAVA Therapeutics, a Nasdaq-listed biotechnology company in Utrecht and Philadelphia, PA. He advises start-up biotechnology companies and pharma on therapeutic antibody development and patents. He is an Operational Partner at Gilde Healthcare in Utrecht. He is also a member of the Board of Directors of the non-profit organization The Antibody Society and a member of the Scientific Advisory Boards of the annual Antibody Engineering and Therapeutics conferences in US and EU, Keystone Symposia on Molecular and Cellular Biology, and the Viral Immunotherapeutic Consortium, a US NIH-funded international consortium to discover and deliver antibody therapeutics against multiple families of emerging infectious diseases. He is a member of the External Advisory Group for the Scientific Research Partnership for Neglected Tropical Snakebite (SRPNTS) program sponsored by the UK Department for International Development.
Immune recognition
The chair is aimed at increasing understanding of the molecular mechanisms of immune recognition and stimulate the translation of research findings into applications, therapies and valorisation.
Paul Parren’s research focusses on the studying antibody biology at the molecular level and translating these findings to applications in the clinic. These applications encompass (clinically) validated innovated antibody technologies that allow antibody therapeutics to be developed in novel formats, thereby providing novel treatment modalities that aim to increase treatment efficacy, ultimately leading to cures for life-threatening and debilitating diseases.
Academic career
Paul Parren studied Biology at the University of Amsterdam with a B.S. in Chemical Biology in 1984 and a M.Sc. in Experimental Oncology (cum laude) in 1987. He did his graduate work in the department of Autoimmune Diseases at the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service in Amsterdam studying crosstalk between recombinant (human) antibodies and innate effector mechanisms with Prof. Lucien Aarden. On June 12, 1992 he received a PhD from the University of Amsterdam after he defended his thesis entitled: “Recombinant antibodies to CD3”. Next, he was a Postdoc at Baxter Diagnostics in Miami, FL where he studied recombinant T-cell receptors and a Postdoc, Assistant Professor and Associate Professor in the department of Immunology at The Scripps Research Institute in La Jolla, California, where he interrogated the human antibody response in protection against viral infections including HIV-1 and Ebola virus. From 2002-2017, he served in the positions of Vice President, Senior Vice President and Scientific Director at the biotechnology company Genmab in Utrecht, where he headed preclinical R&D. Between 2013-2018, he was an Adjunct Honorary Professor of Translational Cancer Research at the University of Southern Denmark in Odense. In 2015, he became a Professor of Molecular Immunology at the Leiden University Medical Center in Leiden, and on 14 September 2018 he spoke his inaugural lecture entitled: “Our immune system: a source of inspiration for innovative drug research”. In 2018, he became head of R&D at the biotech Lava Therapeutics to develop novel bispecific gamma-delta T-cell engagers for cancer therapy. He also provides drug development, patent and investment advice as an independent biotech consultant.
Prof. Parren is dedicated to translate antibody biology and immunotherapy knowledge into innovative therapeutics and technologies. He has a passion for investigating and understanding structure-function relationships and translating the knowledge gained into immunotherapy applications and drug development. He is an inventor of the therapeutic antibodies ofatumumab (Arzerra, Kesimpta) daratumumab (DARZALEX), teprotumumab (Tepezza), tisotumab vedotin (Tivdak) en amivantamab (Rybrevant). Ofatumumab was approved in 2009 for the treatment of Chronic Lymphocytic Leukemia and in 2020 in a subcutaneous formulation for Multiple Sclerosis. Ofatumumab received the Dutch Galenus Prize in 2011 for most innovative new medicine. Ofatumumab (Arzerra) has, for the treatment of cancer, since been transitioned to compassionate use and oncology access programs. Daratumumab was first approved in 2015 for the treatment of Multiple Myeloma. Teprotumumab was approved for the treatment of Active Thyroid Eye Disease (Graves’ orbitopathy in 2020. Tisotumab vedotin (an antibody-drug conjugate) and amivantamab (an EGFR-cMet bispecific antibody) were approved in 2021 by FDA for the treatment of recurrent or metastatic cervical cancer and for metastatic NSCLC with EGFR exon 20 insertion, respectively. Paul Parren further invented and developed several clinically translated technologies aimed at improving antibody therapy, including bispecific antibodies and effector function-enhanced antibodies (DuoBody and HexaBody platforms). The first bispecific antibody product based on the DuoBody technology obtained regulatory approval in 2021. His work has thus far directly led to four therapeutic antibodies that received FDA Breakthrough Therapy designation and ten further therapeutic antibodies in various formats currently in clinical development for the treatment of cancer and Parkinson’s disease.
Prof. Parren supports antibody-related research in the LUMC dept. of Immunology and beyond, with the aim to stimulate the implementation of state-of-the-art antibody technologies in drug development and to innovate, translate and disseminate and valorise (therapeutic) antibody knowledge.
Prizes and honourable appointments
Paul Parren has published extensively both in the scientific as well as the patent literature. He authored over 230 scientific publications with a total of >32,500 citations (Google Scholar). He edited issues of Current Opinion in Immunology (2008 & 2016) and Methods (2014). He in inventor on 60 issued patent families that resulted in 92 US and 56 EU patents and numerous patents in other countries. In total, he is a named inventor on 87 published PCT patent applications. He chaired sessions at 50+ scientific conferences and gave over 200 invited oral presentations at international scientific and business conferences including 15 plenary keynote lectures. In 2017, he received the Utrecht award for excellence in Pharmaceutical Science.
Paul Parren initiated and organized the Dutch Complement Symposium and the European Antibody Engineering and Therapeutics conference
Professor Molecular Immunology
- Faculteit Geneeskunde
- Divisie 4
- Immunologie
- IHB Moleculaire Biologie
- Wulp, W. van der; Gram, A.M.; Bleijlevens, B.; Hagedoorn, R.S.; Araman, C.; Kim, R.Q.; Drijfhout, J.W.; Parren, P.W.H.I.; Hibbert, R.G.; Hoeben, R.C.; Kasteren, S.I. van; Schuurman, J.; Ressing, M.E. & Heemskerk, M.H.M. (2023), Comparison of methods generating antibody-epitope conjugates for targeting cancer with virus-specific T cells, Frontiers in Immunology 14.
- Oostindie, S.C.; Lazar, G.A.; Schuurman, J. & Parren, P.W.H.I. (2022), Avidity in antibody effector functions and biotherapeutic drug design, Nature Reviews Drug Discovery 21(10): 715-735.
- Kampen, M.D. van; Kuipers-De Wilt, L.H.A.M.; Egmond, M.L. van; Reinders-Blankert, P.; Bremer, E.T.J. van den; Wang, G.B.; Heck, A.J.R.; Parren, P.W.H.I.; Beurskens, F.J.; Schuurman, J. & Jong, R.N. de (2022), Biophysical characterization and stability of modified IgG1 antibodies with different hexamerization propensities, Journal of Pharmaceutical Sciences 111(6): 1587-1598.
- Gruijs, M.; Braster, R.; Overdijk, M.B.; Hellingman, T.; Verploegen, S.; Korthouwer, R.; Wilk, B.J. van der; Parren, P.W.H.I.; Vliet, H.J. van der; Boegels, M. & Egmond, M. van (2022), Epidermal growth factor receptor as target for perioperative elimination of circulating colorectal cancer cells, Journal of Oncology 2022.
- Zwarthoff, S.A.; Widmer, K.; Kuipers, A.; Strasser, J.; Ruyken, M.; Aerts, P.C.; Haas, C.J.C. de; Ugurlar, D.; Boer, M.A. den; Vidarsson, G.; Strijp, J.A.G. van; Gros, P.; Parren, P.W.H.I.; Kessel, K.P.M. van; Preiner, J.; Beurskens, F.J.; Schuurman, J.; Ricklin, D. & Rooijakkers, S.H.M. (2021), C1q binding to surface-bound IgG is stabilized by C1r(2)s(2) proteases, Proceedings of the National Academy of Sciences 118(26).
- Vergoossen, D.L.E.; Plomp, J.J.; Gstottner, C.; Fillie-Grijpma, Y.E.; Augustinus, R.; Verpalen, R.; Wuhrer, M.; Parren, P.W.H.I.; Dominguez-Vega, E.; Maarel, S.M. van der; Verschuuren, J.J. & Huijbers, M.G. (2021), Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis, Proceedings of the National Academy of Sciences 118(13).
- Weerdt, I. de; Lameris, R.; Ruben, J.M.; Boer, R. de; Kloosterman, J.; King, L.A.; Levin, M.D.; Parren, P.W.H.I.; Gruijl, T.D. de; Kater, A.P. & Vliet, H.J. van der (2021), A bispecific single-domain antibody boosts autologous V gamma 9V delta 2-T cell responses toward CD1d in chronic lymphocytic leukemia, Clinical Cancer Research 27(6): 1744-1755.
- Weerdt, I. de; Lameris, R.; Scheffer, G.L.; Vree, J.; Boer, R. de; Stam, A.G.; Ven, R. van de; Levin, M.D.; Pals, S.T.; Roovers, R.C.; Parren, P.W.H.I.; Gruijl, T.D. de; Kater, A.P. & Vliet, H.J. van der (2021), A bispecific antibody antagonizes prosurvival CD40 signaling and promotes V gamma 9V delta 2 T cell-mediated antitumor responses in human B-cell malignancies, Cancer Immunology Research 9(1): 50-61.
- Neijssen, J.; Cardoso, R.M.F.; Chevalier, K.M.; Wiegman, L.; Valerius, T.; Anderson, G.M.; Moores, S.L.; Schuurman, J.; Parren, P.W.H.I.; Strohl, W.R. & Chiu, M.L. (2021), Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET, Journal of Biological Chemistry 296.
- Overdijk, M.B.; Strumane, K.; Beurskens, F.J.; Buijsse, A.O.; Vermot-Desroches, C.; Vuillermoz, B.S.; Kroes, T.; Jong, B. de; Hoevenaars, N.; Hibbert, R.G.; Lingnau, A.; Forssmann, U.; Schuurman, J.; Parren, P.W.H.I.; Jong, R.N. de & Breij, E.C.W. (2020), Dual epitope targeting and enhanced hexamerization by DR5 antibodies as a novel approach to induce potent antitumor activity through DR5 agonism, Molecular Cancer Therapeutics 19(10): 2126-2138.
- Koning, M.T.; Vletter, E.M.; Rademaker, R.; Vergroesen, R.D.; Trollmann, I.J.M.; Parren, P.; Bergen, C.A.M. van; Scherer, H.U.; Kielbasa, S.M.; Toes, R.E.M. & Veelken, H. (2020), Templated insertions at VD and DJ junctions create unique B-cell receptors in the healthy B-cell repertoire, European Journal of Immunology 50(12).
- Oostindie, S.C.; Horst, H.J. van der; Kil, L.P.; Strumane, K.; Overdijk, M.B.; Brink, E.N. van den; Brakel, J.H.N. van den; Rademaker, H.J.; Kessel, B. van; Noort, J. van den; Chamuleau, M.E.D.; Mutis, T.; Lindorfer, M.A.; Taylor, R.P.; Schuurman, J.; Parren, P.W.H.I.; Beurskens, F.J. & Breij, E.C.W. (2020), DuoHexaBody-CD37(R), a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies, Blood Cancer Journal 10(3).
- Strasser, J.; Jong, R.N. de; Beurskens, F.J.; Schuurman, J.; Parren, P.W.H.I.; Hinterdorfer, P. & Preiner, J. (2020), Weak fragment crystallizable (Fc) domain interactions drive the dynamic assembly of IgG oligomers upon antigen recognition, ACS Nano 14(3): 2739-2750.
- Engelberts, P.J.; Hiemstra, I.H.; Jong, B. de; Schuurhuis, D.H.; Meesters, J.; Hernandez, I.B.; Oostindie, S.C.; Neijssen, J.; Brink, E.N. van den; Horbach, G.J.; Verploegen, S.; Labrijn, A.F.; Salcedo, T.; Schuurman, J.; Parren, P.W.H.I. & Breij, E.C.W. (2020), DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing, EBioMedicine 52.
- Lubbers, R.; Oostindie, S.C.; Dijkstra, D.J.; Parren, P.W.H.I.; Verheul, M.K.; Abendstein, L.; Sharp, T.H.; Ru, A. de; Janssen, G.M.C.; Veelen, P.A. van; Bremer, E.T.J. van den; Bleijlevens, B.; Kreuk, B.J. de; Beurskens, F.J. & Trouw, L.A. (2020), Carbamylation reduces the capacity of IgG for hexamerization and complement activation, Clinical and Experimental Immunology 200(1).
- Koopman, L.A.; Terp, M.G.; Zom, G.G.; Janmaat, M.L.; Jacobsen, K.; Gresnigt-van den Heuve, E.; Brandhorst, M.; Forssmann, U.; Bree, F. de; Pencheva, N.; Lingnau, A.; Zipeto, M.A.; Parren, P.W.H.I.; Breij, E.C.W. & Ditzels, H.J. (2019), Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer.
- Oostindie, S.C.; Horst, H.J. van der; Lindorfer, M.A.; Cook, E.M.; Tupitza, J.C.; Zent, C.S.; Burack, R.; VanDerMeid, K.R.; Strumane, K.; Chamuleau, M.E.D.; Mutis, T.; Jong, R.N. de; Schuurman, J.; Breij, E.C.W.; Beurskens, F.J.; Parren, P.W.H.I. & Taylor, R.P. (2019), CD20 and CD37 antibodies synergize to activate complement by Fc-mediated clustering, Haematologica 104(9): 1841-1852.
- Kramer, C.S.M.; Franke-van Dijk, M.E.I.; Priddey, A.J.; Pongracz, T.; Gnudi, E.; Car, H.; Karahan, G.E.; Beelen, E. van; Zilvold-van den Oever, C.C.C.; Rademaker, H.J.; Haan, N. de; Wuhrer, M.; Kosmoliaptsis, V.; Parren, P.W.H.I.; Mulder, A.; Roelen, D.L.; Claas, F.H.J. & Heidt, S. (2019), Recombinant human monoclonal HLA antibodies of different IgG subclasses recognising the same epitope: Excellent tools to study differential effects of donor-specific antibodies, HLA: Immune Response Genetics.
- Labrijn, A.F.; Janmaat, M.L.; Reichert, J.M. & Parren, P.W.H.I. (2019), Bispecific antibodies: a mechanistic review of the pipeline, Nature Reviews Drug Discovery 18(8): 585-608.
- Strasser, J.; Jong, R.N. de; Beurskens, F.J.; Wang, G.B.; Heck, A.J.R.; Schuurman, J.; Parren, P.W.H.I.; Hinterdorfer, P. & Preiner, J. (2019), Unraveling the Macromolecular Pathways of IgG Oligomerization and Complement Activation on Antigenic Surfaces, Nano Letters 19(7): 4787-4796.
- Donk, N.W.C.J. van de; Casneuf, T.; Cara, A. di; Parren, P.W.; Zweegman, S.; Kessel, B. van; Lokhorst, H.M.; Usmani, S.Z.; Lonial, S.; Richardson, P.G.; Chiu, C.; Mutis, T.; Nijhof, I.S. & Sasser, A.K. (2019), Impact of Fc gamma receptor polymorphisms on efficacy and safety of daratumumab in relapsed/refractory multiple myeloma.
- Engelberts, P.J.; Breij, E.C.W.; Valerius, T.; Schuurman, J.; Parren, P.W.H.I. & Beurskens, F.J. (2018), Response to Comment on "Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells".
- Boshuizen, J.; Koopman, L.A.; Krijgsman, O.; Shahrabi, A.; Gresnigt-van den Heuvel, E.; Ligtenberg, M.A.; Vredevoogd, D.W.; Kemper, K.; Kuilman, T.; Song, J.Y.; Pencheva, N.; Mortensen, J.T.; Foppen, M.G.; Rozeman, E.A.; Blank, C.U.; Janmaat, M.L.; Satijn, D.; Breij, E.C.W.; Peeper, D.S. & Parren, P.W.H.I. (2018), Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors, Nature Medicine 24(2): 203-+.
- Ugurlar, D.; Howes, S.C.; Kreuk, B.J. de; Koning, R.I.; Jong, R.N. de; Beurskens, F.J.; Schuurman, J.; Koster, A.J.; Sharp, T.H.; Parren, P.W.H.I. & Gros, P. (2018), Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement, Science 359(6377): 794-797.
- Riedl, T.; Boxtel, E. van; Bosch, M.; Parren, P.W.H.I. & Gerritsen, A.F. (2016), High-Throughput Screening for Internalizing Antibodies by Homogeneous Fluorescence Imaging of a pH-Activated Probe, Journal of Biomolecular Screening 21(1): 12-23.
- Groot, N.G. de; Heijmans, C.M.C.; Wiel, M.K.H. van der; Blokhuis, J.H.; Mulder, A.; Guethlein, L.A.; Doxiadis, G.G.M.; Claas, F.H.J.; Parham, P. & Bontrop, R.E. (2016), Complex MHC Class I Gene Transcription Profiles and Their Functional Impact in Orangutans, Journal of Immunology 196(2): 750-758.
- Jones, T.D.; Carter, P.J.; Pluckthun, A.; Vasquez, M.; Holgate, R.G.E.; Hotzel, I.; Popplewell, A.G.; Parren, P.W.H.I.; Enzelberger, M.; Rademaker, H.J.; Clark, M.R.; Lowe, D.C.; Dahiyat, B.I.; Smith, V.; Lambert, J.M.; Wu, H.; Reilly, M.; Haurum, J.S.; Dubel, S.; Huston, J.S.; Schirrmann, T.; Janssen, R.A.J.; Steegmaier, M.; Gross, J.A.; Bradbury, A.R.M.; Burton, D.R.; Dimitrov, D.S.; Chester, K.A.; Glennie, M.J.; Davies, J.; Walker, A.; Martin, S.; McCafferty, J. & Baker, M.P. (2016), The INNs and outs of antibody nonproprietary names, mAbs 8(1): 1-9.
- Parren, P.W.H.I.; Burton, D.R.; Bradbury, A.; Huston, J.S.; Carter, P.J.; Veldman, T.; Chester, K.A.; Larrick, J.W.; Alfenito, M.R.; Scott, J.K.; Weiner, L.M.; Adams, G.P. & Reichert, J.M. (2015), Antibody Engineering & Therapeutics 2015: The Antibody Society's annual meeting December 7-10, 2015, San Diego, CA, mAbs 7(6): 981-988.
- Melis, J.P.M.; Strumane, K.; Ruuls, S.R.; Beurskens, F.J.; Schuurman, J. & Parren, P.W.H.I. (2015), Complement in therapy and disease Regulating the complement system with antibody-based therapeutics, Molecular Immunology 67(2): 117-130.
- Parren P.W.H.I. (14 September 2015). Ons afweersysteem: een inspiratiebron voor vernieuwend geneesmiddelenonderzoek. Leids Universitair Medisch Centrum, Medicine, Leiden. Leiden. [inaugural address].
- Bremer, E.T.J. van den; Beurskens, F.J.; Voorhorst, M.; Engelberts, P.J.; Jong, R.N. de; Boom, B.G. van der; Cook, E.M.; Lindorfer, M.A.; Taylor, R.P.; Berkel, P.H.C. van & Parren, P.W.H.I. (2015), Human IgG is produced in a pro-form that requires clipping of C-terminal lysines for maximal complement activation, mAbs 7(4): 672-680.
- Oostendorp, M.; Bueren, J.J.L. van; Doshi, P.; Khan, I.; Ahmadi, T.; Parren, P.W.H.I.; Solinge, W.W. van & Vooght, K.M.K. de (2015), When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy, Transfusion 55(6): 1555-1562.
- Dyachenko, A.; Wang, G.B.; Belov, M.; Makarov, A.; Jong, R.N. de; Bremer, E.T.J. van den; Parren, P.W.H.I. & Heck, A.J.R. (2015), Tandem Native Mass-Spectrometry on Antibody-Drug Conjugates and Submillion Da Antibody-Antigen Protein Assemblies on an Orbitrap EMR Equipped with a High-Mass Quadrupole Mass Selector, Analytical Chemistry 87(12): 6095-6102.
- Goeij, B.E.C.G. de; Satijn, D.; Freitag, C.M.; Wubbolts, R.; Bleeker, W.K.; Khasanov, A.; Zhu, T.; Chen, G.; Miao, D.; Berkel, P.H.C. van & Parren, P.W.H.I. (2015), High Turnover of Tissue Factor Enables Efficient Intracellular Delivery of Antibody-Drug Conjugates, Molecular Cancer Therapeutics 14(5): 1130-1140.
- Overdijk, M.B.; Verploegen, S.; Bogels, M.; Egmond, M. van; Bueren, J.J.L. van; Mutis, T.; Groen, R.W.J.; Breij, E.; Martens, A.C.M.; Bleeker, W.K. & Parren, P.W.H.I. (2015), Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma, mAbs 7(2): 311-320.
- Bradbury, A. & Pluckthun, A. (2015), Standardize antibodies used in research, Nature 518(7537): 27-29.
- Board Member and Chairperson