Inger Sandlie

Image of Inger Sandlie
Norwegian version of this page
Phone +47 22854568
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Visiting address Blindernveien 31 0371 Oslo
Postal address Postboks 1066 Blindern 0316 Oslo
Other affiliations Department of Biosciences

My research group has studied structure and function of antibodies and T-cell receptors and engineered these specific immune system detectors for use in therapy and as research tools. I am particularly interested in the interaction of both molecules with their specific receptors. Furthermore, my research group unraveled how albumin and IgG share an intracellular receptor, FcRn, that regulates the serum half-life and biodistribution of both.

I received my PhD from the University of Bergen in 1981 in the field of DNA and nucleotide synthesis. I then held postdoctoral positions at Johns Hopkins University and the Radium Hospital in Oslo, where I started my studies of antibody structure and function. I joined UiO in 1988, first as assistant professor in Molecular Biology and then, in 1995, as full professor. From 2007-2017 I was deputy director of the Centre for Immune Regulation, a Centre of Excellence appointed by the Research Council of Norway and held a position as senior researcher at Oslo University Hospital (OUH). 2017-2020, I was deputy director of a Federation of Clinical Immunology Societies Centre of Excellence, consisting of 18 research groups located in Oslo, and president of the Norwegian Society for Immunology.

I have co-authored more than 130 publications since 1988, and have received awards for scientific innovation. I am co-inventor on a number of patents describing antibody variants and ”Vaccibodies”, ”Phagemers” and the ”Veltis®” technology and co-founder of two biotechnology companies: Vaccibody A/S and Nextera A/S. I have consulted for Vaccibody A/S (Norway), Albumedix A/S (UK) and for Syntimmune A/S (USA), and presently serve on the board of the technology transfer office of UiO and OUH (Inven2 A/S) and Radforsk. I am member of the Advisory Board for OUH Comprehensive Cancer Centre and Lund University’s board for research evaluation. Furthermore, I have served on boards at the Norwegian Research Council, consulted for the Swedish and Finnish research councils and been member of the Norwegian Biotechnology Advisory Board.

I was elected member of the Norwegian Academy of Science and Letters in 2002, and served as group leader (Cell Biology) from 2011-2019. 

I have supervised more than 60 MSc students and 20 PhD students, and have evaluated doctoral degrees in Norway, Sweden, Switzerland and Australia. I was on a 3 months sabbatical at Brigham and Womens’s Hospital and Harvard Medical School, Boston in 2015, and at the Scripps Research Institute, La Jolla in 2016. 

Contributions to Science the last 10 years

Immunoreceptor engineering:

We have established a novel phage display platform, socalled Signal Sequence Independent phage display – SSIp display. The key finding is that two viral capsid proteins, pVII and pIX, display fusion proteins extremely well, and they do so without the need for translational signal sequences (Nilssen NR et al, Nucleic Acids Res 2012 and Løset GÅ et al, PLoS One 2011). Importantly, we have found that the SSIp display phage particles can display not only antibody fragments and T cell receptors (Høydahl LS et al, Sci Reports 2016 and Gunnarsen KS et al, Sci Reports 2013), but also MHC class II peptide complexes, and we call the MHC class II displaying phages “Phagemers”. Phagemers bind to specific T cell receptors, and thus detect T cells based on this specificity. We have explored the use of Phagemers as diagnostic tools. SSIp display is the core technology of the spin-out company Nextera A/S (www.nextera.no). Nextera A/S commercializes and develops the Phagemer technology and selects binders from large phagemer libraries, the aim being target discovery for drug development.

Studies of celiac disease:

Celiac disease (CD) develops in individuals with certain MHC class II types, and in particular, DQ2.5, which is characterized by its ability to bind and present modified gluten peptides on the surface of antigen presenting cells. To answer questions regarding the nature of these antigen presenting cells in the gut of CD patients, we designed antibodies that bind gluten-DQ2.5 complexes with very high specificity, using SSIp display. In collaboration with Ludvig Sollid and Frode Jahnsens groups, we then found the antibodies to bind B cells and plasma cells in patient biopsies.  We hypothesize that the interaction between these cells and disease-associated T cells is a key driver of disease, as the detecting antibodies also inhibit T cell activation and are drug candidates. CD patients produce autoantibodies against transglutaminase 2, the enzyme that modifies the gluten peptides. Interestingly, at least some of the gluten-DQ2.5 presenting plasma cells are transglutaminase 2 specific (Høydahl LS et al, Gastroenterology 2019 and Frick R et al, Science Immunology 2021).

The T cell response against gluten-DQ2.5 complexes is biased in CD patients, in that their T cell receptors are often composed of signature variable segment pairs selected for being particularly well suited for complex binding. In collaboration with Ludvig Sollid and Shuo Wang Qiao, we have unraveled the molecular basis for a common signature, and identified an MHC recognition motif centered on a certain amino acid residue in the T cell receptor. This one residue not only contacts MHC, but also directs a pivotal part of the T cell receptor to contact the gluten peptide (Gunnarsen KS et al, JCI Insight 2017).

Half-life of IgG antibodies and albumin fused drugs:

Most proteins in blood degrade within a few hours or days, but IgG and albumin, which are the two most abundant, are rescued from degradation and have half-lives of three weeks. This is due to the fact that they bind the neonatal Fc receptor (FcRn), and we study how FcRn binding regulates the serum half-life and biodistribution of both ligands.

The long half-life is important for the therapeutic success of IgG antibodies, and thus, there is an intense interest in increasing the strength of the FcRn interaction to prolong the half-life even further. The FcRn interaction is pH dependent, with histidine dependent strong binding at acidic pH and little or no binding at neutral pH. We have studied how FcRn binds IgG molecules of different subclasses, and found that members of the IgG3 subclass degrade faster than the others because of a slight alteration in FcRn binding kinetics (Stapleton NM et al, Nat Commun 2011). This is due to a single amino acid being arginine in IgG3 and histidine in the other subclasses. We have also engineered an IgG variant with increased binding at acidic pH, which has enhanced half-life as well as ability to activate complement (PCT/IB2017/000327). The patent was recently licensed by a large drug development company.

We have also unraveled the interaction between FcRn and albumin (Andersen JT et al, Nat Commun 2012). Again, it is pH and histidine dependent as well as largely hydrophobic in nature (Sand KMK et al, J Biol Chem 2014). We have designed albumin variants with increased binding to FcRn at acidic pH that have increased half-life in rodents and monkeys (Andersen JT et al, J Biol Chem 2014 and described in several patents). Our invention, The Veltis ®technology (albumin attachment to drugs) is commercialized by Albumedix A/S, a collaborating drug development company, and involves both normal albumin and our engineered albumin variants.

Biodistribution of IgG antibodies

FcRn is expressed intracellularly, and binds IgG taken up by fluid-phase endocytosis. It can then direct monomeric IgG to the surface of the opposite side of the cell (transcytosis) or to the side of entry (recycling). We have studied both processes using the natural ligands as well as engineered variants (Foss S et al, J Control Release 2016).

A new in vitro recycling assay designed by us predicts the behavior of designed FcRn-binding molecules in vivo in animal models (Grevys A et al, Nat Commun 2017). We have found that FcRn is the only Fc receptor required for transport of IgG across cellular barriers and placenta (Mathiesen et al, Blood 2013).

In collaboration with Richard Blumberg’s laboratory, we have found that it enhances antigen presentation and cross presentation of antigen in immune complexes by specialized dendritic cells (Baker K et al, Proc Natl Acad Sci 2011). Furthermore, we recently found that FcRn cooperates with FcγRIIa to regulate innate cytokine production and antigen presentation through formation of a ternary complex consisting of FcRn, FcγRIIa and IgG IC (Hubbard J et al, J Exp Med 2020).

Biodistribution of albumin and albumin fused drugs  

In collaboration with Richard Blumberg’s laboratory, we found that albumin produced in the liver is released to the bloodstream, and directed away from the bile (Pyzik M et al, Proc Natl Acad Sci 2017). 

Importantly, we recently found that albumin is transcytosed efficiently from the apical to the basolateral side of the mucosae, and think this observation holds great promise for mucosal delivery of albumin based vaccines and therapeutics (Bern M et al, J Control Release 2015 and Science Translational Med 2020).

Previous positions

2017-2020, Deputy Director of a Federation of Clinical Immunology Societies Centre of Excellence

2007- 2017 Deputy Director of Centre for Immune Regulation, UiO

1995- 2020 Professor of Molecular Biology, Department of Biosciences, UiO

1988-1995 Assistant professor, Department of Biology, UiO

1985-1988 Researcher, Norwegian Radium Hospital, Oslo

1982-1984 Postdoc, Department of Biochemistry, Johns Hopkins University, MD, USA

Honors and Memberships

2016- Honorary member of the Norwegian Society for Immunology

2015- Innovation prize from Inven2

2011- First Innovation prize awarded by UiO 

2007- Member of Henry Kunkel Society, Rockefeller University, USA

2003- Innovation prize from Medinnova for “Vaccibodies”

2002- Elected member of the Norwegian Academy of Science and Letters. Group leader (Cell Biology) 2011-2019  

1996- Innovation prize for “Troybodies”

Other Experience 

2017-2020 President of the Norwegian Society for Immunology

2014- 2019 Scientific Advisory Board member: Syntimmune A/S, Vaccibody A/S, Albumedix A/S

2010- present Board member Inven2 A/S  and Radforsk

2006- 2020 Reviewer Swedish and Finnish Research Councils

2004- 2020 PhD thesis opponent in Norway, Sweden, Denmark, Switzerland and Australia

1998- 2000 Member of the Norwegian Biotechnology Advisory Board

1995-  Member Advisory Boards at The Norwegian Research Council  

Patents and industrialisation

Coinventor on 16 patents granted or pending on modified antibodies and albumin variants. Cofounder of Vaccibody A/S (https://www.vaccibody.com) and Nextera A/S (https://nextera.no).

Publications

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  • Andersen, Jan Terje & Sandlie, Inger (2011). Pharmacokinetics of IgG and albumin: The impact of FcRn for Design of Drug Delivery Systems: The impact of FcRn for Design of Drug Delivery Systems. Wiley-VCH Verlag GmbH. ISBN 9783527328239. 34 p.
  • Andersen, Jan Terje & Sandlie, Inger (2011). Extending Antibody Half Lives with Albumin In: Recombinant Antibodies for Immunotherapy. Cambridge University Press. ISBN 9780521887328. 17 p.
  • Andersen, Jan Terje; Sandlie, Inger; Kenanova, Vania E; Olafsen, Tove & Wu, Anna M (2010). Engineering of the Fc Region for Improved PK (FcRn interaction. Springer-Verlag Berlin Heidelberg . ISBN 978-3-642-01143-6. 19 p.

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  • Andersen, Jan Terje; Sakya, Siri Aastedatter; Foss, Stian; Sandlie, Inger & Voets, Ardi (2019). Is an HIV vaccine within reach? Vaksinebloggen.
  • Andersen, Jan Terje; Sakya, Siri Aastedatter; Foss, Stian & Sandlie, Inger (2019). Hvordan kan moderne medisin forebygge HIV? Medisinbloggen.
  • Shaw, Alan; Hoffecker, Ian T.; Smyrlaki, Ioanna; Rosa, João; Grevys, Algirdas & Bryant-Bratlie, Diane Lynn [Show all 10 contributors for this article] (2019). Publisher Correction: Binding to nanopatterned antigens is dominated by the spatial tolerance of antibodies. Nature Nanotechnology. ISSN 1748-3387. 14(4), p. 398–398. doi: 10.1038/s41565-019-0404-3.
  • Sandlie, Inger; Graver, Hans Petter & Frich, Jan C (2017). Mindre midlertidighet. Klassekampen. ISSN 0805-3839. p. 24–24.
  • Frich, Jan C; Graver, Hans Petter & Sandlie, Inger (2017). Slik skal team Graver, Sandlie & Frich gjøre UiO til læringsuniversitetet. Uniforum. ISSN 1891-5825.
  • Graver, Hans Petter; Sandlie, Inger & Frich, Jan C (2017). Forvandle vår verden | Graver, Sandlie og Frich. Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116. p. 18–19.
  • Frich, Jan C; Graver, Hans Petter & Sandlie, Inger (2017). Slik blir Team Gravers læringsstrategi. Universitas. ISSN 0805-1798.
  • Frich, Jan C; Graver, Hans Petter & Sandlie, Inger (2017). Hvorfor begrunne karakteren? Universitas. ISSN 0805-1798.
  • Graver, Hans Petter; Sandlie, Inger & Frich, Jan C (2017). Rektorteam Graver/Sandlie/Frich: Ledelse og administrasjon. Uniforum. ISSN 1891-5825.
  • Mandecki, W.; Goldman, E.; Sandlie, Inger & Løset, Geir Åge (2015). Phage Display and Selection of Protein Ligands. In Goldman, Emanuel & Green, Laurence (Ed.), Practical Handbook of Microbiology, Third Edition. CRC Press. ISSN 9781466587397. p. 101–114.
  • Lau, Corinna; Gunnarsen, Kristin Støen; Høydahl, Lene Støkken; Berntzen, Gøril; Stokes, Christopher R. & Espevik, Terje [Show all 8 contributors for this article] (2012). Recombinant anti-human and anti-porcine CD14 antibodies. Immunobiology. ISSN 0171-2985. 217(11), p. 1197–1198. doi: 10.1016/j.imbio.2012.08.196.
  • Høydahl, Lene Støkken; Neumann, Ralf Stefan; Qiao, Shuo Wang; Sollid, Ludvig Magne; Sandlie, Inger & Løset, Geir Åge (2011). Development of a High Affinity TCR Reagent by Phage Display to Study Antigen Presentation in Celiac Disease. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), p. 372–372.
  • Gunnarsen, Kristin Støen; Kristinsson, Solveig Gunn; Bogen, Bjarne; Sandlie, Inger & Løset, Geir Åge (2011). Thermostability Engineering of a Soluble Single Chain T Cell Receptor (scTCR) Using Phage Display. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), p. 352–352.
  • Qiao, Shuo Wang; Raki, Melinda; Gunnarsen, Kristin Støen; Løset, Geir Åge; Sandlie, Inger & Sollid, Ludvig Magne (2011). Post-Translational Modification of Gluten Shapes the T Cell Response in Coeliac Disease by Direct Interaction with the T Cell Receptor. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), p. 356–356.
  • Foss, Stian; Michaelsen, Terje Einar; Sandlie, Inger & Andersen, Jan Terje (2011). The Influence of Removal of the IgG Fab Arms on Binding to FcRn. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), p. 350–351. doi: 10.1111/j.1365-3083.2011.02516.x.
  • Qiao, Shuo Wang; Raki, Melinda; Løset, Geir Åge; Sandlie, Inger & Sollid, Ludvig Magne (2010). TCR Vbeta Bias and Semi-Public T Cell Responses In DQ2-Gliadin-Alpha-II Specific T Cells From Coeliac Disease Patients. Scandinavian Journal of Immunology. ISSN 0300-9475. 71(6), p. 511–+.
  • Gunnarsen, Kristin Støen; Kristinsson, Solveig Gunn; Bogen, Bjarne; Sandlie, Inger & Løset, Geir Åge (2009). Thermostability engineering of a soluble single chain T cell receptor using phage display.
  • Michaelsen, Terje Einar; Emilsen, S; Sandlie, I; Bratlie, Diane Lynn Bryant; Langerud, Beathe Kiland & Ihle, Øistein (2009). Human secretory IgM and serum IgM can activate complement equally well.
  • Andersen, JT; Daba, Muluneh B; Berntzen, G; Michaelsen, Terje Einar & Sandlie, I (2009). Cross-species binding analyses of mouse and human neonatal Fc receptor with their ligands. Implications for evaluations of therapeutic antibodies and albumin fusions.
  • Andersen, Jan Terje & Sandlie, Inger (2011). FcRn regulates the pharmacokinetics of albumin. Sojo University Publishing.

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Published Nov. 4, 2010 2:48 PM - Last modified Oct. 29, 2021 2:57 PM