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Therapeutic targeting of the complement system.

Ricklin D, Mastellos DC, Lambris JD.

Nat Rev Drug Discov. 2019 Dec 9. doi: 10.1038/s41573-019-0055-y. [Epub ahead of print] No abstract available.


Author Correction: 'Stealth' corporate innovation: an emerging threat for therapeutic drug development.

Mastellos DC, Blom AM, Connolly ES, Daha MR, Geisbrecht BV, Ghebrehiwet B, Gros P, Hajishengallis G, Holers VM, Huber-Lang M, Kinoshita T, Mollnes TE, Montgomery RA, Morgan BP, Nilsson B, Pio R, Ricklin D, Risitano AM, Taylor RP, Mantovani A, Ioannidis JPA, Lambris JD.

Nat Immunol. 2019 Nov;20(11):1556. doi: 10.1038/s41590-019-0531-x.


'Stealth' corporate innovation: an emerging threat for therapeutic drug development.

Mastellos DC, Blom AM, Connolly ES, Daha MR, Geisbrecht BV, Ghebrehiwet B, Gros P, Hajishengallis G, Holers VM, Huber-Lang M, Kinoshita T, Mollnes TE, Montgomery RA, Morgan BP, Nilsson B, Pio R, Ricklin D, Risitano AM, Taylor RP, Mantovani A, Ioannidis JPA, Lambris JD.

Nat Immunol. 2019 Nov;20(11):1409-1413. doi: 10.1038/s41590-019-0503-1. No abstract available. Erratum in: Nat Immunol. 2019 Oct 11;:.


Clinical promise of next-generation complement therapeutics.

Mastellos DC, Ricklin D, Lambris JD.

Nat Rev Drug Discov. 2019 Sep;18(9):707-729. doi: 10.1038/s41573-019-0031-6. Epub 2019 Jul 19. Review.


Complement C3 inhibition by compstatin Cp40 prevents intra- and extravascular hemolysis of red blood cells.

Baas I, Delvasto-Nuñez L, Ligthart P, Brouwer C, Folman C, Reis ES, Ricklin D, Lambris JD, Wouters D, de Haas M, Jongerius I, Zeerleder SS.

Haematologica. 2020 Jan 31;105(2):e57-e60. doi: 10.3324/haematol.2019.216028. Print 2020. No abstract available.


Native State of Complement Protein C3d Analysed via Hydrogen Exchange and Conformational Sampling.

Devaurs D, Papanastasiou M, Antunes DA, Abella JR, Moll M, Ricklin D, Lambris JD, Kavraki LE.

Int J Comput Biol Drug Des. 2018;11(1-2):90-113. doi: 10.1504/IJCBDD.2018.090834. Epub 2018 Mar 24.


Factor H interferes with the adhesion of sickle red cells to vascular endothelium: a novel disease-modulating molecule.

Lombardi E, Matte A, Risitano AM, Ricklin D, Lambris JD, De Zanet D, Jokiranta ST, Martinelli N, Scambi C, Salvagno G, Bisoffi Z, Colato C, Siciliano A, Bortolami O, Mazzuccato M, Zorzi F, De Marco L, De Franceschi L.

Haematologica. 2019 May;104(5):919-928. doi: 10.3324/haematol.2018.198622. Epub 2019 Jan 10.


Developments in anti-complement therapy; from disease to clinical trial.

Harris CL, Pouw RB, Kavanagh D, Sun R, Ricklin D.

Mol Immunol. 2018 Oct;102:89-119. doi: 10.1016/j.molimm.2018.06.008. Epub 2018 Aug 16. Review.


Protective Effects of the Complement Inhibitor Compstatin CP40 in Hemorrhagic Shock.

van Griensven M, Ricklin D, Denk S, Halbgebauer R, Braun CK, Schultze A, Hönes F, Koutsogiannaki S, Primikyri A, Reis E, Messerer D, Hafner S, Radermacher P, Biglarnia AR, Resuello RRG, Tuplano JV, Mayer B, Nilsson K, Nilsson B, Lambris JD, Huber-Lang M.

Shock. 2019 Jan;51(1):78-87. doi: 10.1097/SHK.0000000000001127.


Correction to: Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy.

Yuan X, Yang M, Chen X, Zhang X, Sukhadia S, Musolino N, Bao H, Chen T, Xu C, Wang Q, Santoro S, Ricklin D, Hu J, Lin R, Yang W, Li Z, Qin W, Zhao A, Scholler N, Coukos G.

Cancer Immunol Immunother. 2018 Feb;67(2):329-339. doi: 10.1007/s00262-017-2101-0.


Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte Aggregate Formation.

Blatt AZ, Saggu G, Cortes C, Herbert AP, Kavanagh D, Ricklin D, Lambris JD, Ferreira VP.

Front Immunol. 2017 Nov 23;8:1586. doi: 10.3389/fimmu.2017.01586. eCollection 2017.


The renaissance of complement therapeutics.

Ricklin D, Mastellos DC, Reis ES, Lambris JD.

Nat Rev Nephrol. 2018 Jan;14(1):26-47. doi: 10.1038/nrneph.2017.156. Epub 2017 Dec 4. Review.


Novel mechanisms and functions of complement.

Hajishengallis G, Reis ES, Mastellos DC, Ricklin D, Lambris JD.

Nat Immunol. 2017 Nov 16;18(12):1288-1298. doi: 10.1038/ni.3858. Review.


Complement-activation fragment C4a mediates effector functions by binding as untethered agonist to protease-activated receptors 1 and 4.

Wang H, Ricklin D, Lambris JD.

Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):10948-10953. doi: 10.1073/pnas.1707364114. Epub 2017 Sep 26.


Complement in cancer: untangling an intricate relationship.

Reis ES, Mastellos DC, Ricklin D, Mantovani A, Lambris JD.

Nat Rev Immunol. 2018 Jan;18(1):5-18. doi: 10.1038/nri.2017.97. Epub 2017 Sep 18. Review.


Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.

Xue X, Wu J, Ricklin D, Forneris F, Di Crescenzio P, Schmidt CQ, Granneman J, Sharp TH, Lambris JD, Gros P.

Nat Struct Mol Biol. 2017 Aug;24(8):643-651. doi: 10.1038/nsmb.3427. Epub 2017 Jul 3.


Complement in clinical medicine: Clinical trials, case reports and therapy monitoring.

Ricklin D, Barratt-Due A, Mollnes TE.

Mol Immunol. 2017 Sep;89:10-21. doi: 10.1016/j.molimm.2017.05.013. Epub 2017 May 31. Review.


Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery.

Mastellos DC, Reis ES, Ricklin D, Smith RJ, Lambris JD.

Trends Immunol. 2017 Jun;38(6):383-394. doi: 10.1016/ Epub 2017 Apr 14.


Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data.

Devaurs D, Antunes DA, Papanastasiou M, Moll M, Ricklin D, Lambris JD, Kavraki LE.

Front Mol Biosci. 2017 Mar 10;4:13. doi: 10.3389/fmolb.2017.00013. eCollection 2017.


Structural Implications for the Formation and Function of the Complement Effector Protein iC3b.

Papanastasiou M, Koutsogiannaki S, Sarigiannis Y, Geisbrecht BV, Ricklin D, Lambris JD.

J Immunol. 2017 Apr 15;198(8):3326-3335. doi: 10.4049/jimmunol.1601864. Epub 2017 Mar 3.


Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation.

Harder MJ, Kuhn N, Schrezenmeier H, Höchsmann B, von Zabern I, Weinstock C, Simmet T, Ricklin D, Lambris JD, Skerra A, Anliker M, Schmidt CQ.

Blood. 2017 Feb 23;129(8):970-980. doi: 10.1182/blood-2016-08-732800. Epub 2016 Dec 27.


Method development and validation for the quantitation of the complement inhibitor Cp40 in human and cynomolgus monkey plasma by UPLC-ESI-MS.

Primikyri A, Papanastasiou M, Sarigiannis Y, Koutsogiannaki S, Reis ES, Tuplano JV, Resuello RR, Nilsson B, Ricklin D, Lambris JD.

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jan 15;1041-1042:19-26. doi: 10.1016/j.jchromb.2016.12.004. Epub 2016 Dec 6.


Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy.

Yuan X, Yang M, Chen X, Zhang X, Sukhadia S, Musolino N, Bao H, Chen T, Xu C, Wang Q, Santoro S, Ricklin D, Hu J, Lin R, Yang W, Li Z, Qin W, Zhao A.

Cancer Immunol Immunother. 2017 Mar;66(3):367-378. doi: 10.1007/s00262-016-1937-z. Epub 2016 Dec 8. Erratum in: Cancer Immunol Immunother. 2018 Jan 8;:.


Complement component C3 - The "Swiss Army Knife" of innate immunity and host defense.

Ricklin D, Reis ES, Mastellos DC, Gros P, Lambris JD.

Immunol Rev. 2016 Nov;274(1):33-58. doi: 10.1111/imr.12500. Review.


Preformed mediators of defense-Gatekeepers enter the spotlight.

Ricklin D, Lambris JD.

Immunol Rev. 2016 Nov;274(1):5-8. doi: 10.1111/imr.12497. No abstract available.


Protection of host cells by complement regulators.

Schmidt CQ, Lambris JD, Ricklin D.

Immunol Rev. 2016 Nov;274(1):152-171. doi: 10.1111/imr.12475. Review.


Compstatin Cp40 blocks hematin-mediated deposition of C3b fragments on erythrocytes: Implications for treatment of malarial anemia.

Lindorfer MA, Cook EM, Reis ES, Ricklin D, Risitano AM, Lambris JD, Taylor RP.

Clin Immunol. 2016 Oct;171:32-35. doi: 10.1016/j.clim.2016.08.017. Epub 2016 Aug 18.


Complement therapeutics.

Ricklin D, Lambris JD.

Semin Immunol. 2016 Jun;28(3):205-7. doi: 10.1016/j.smim.2016.07.001. No abstract available.


From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage.

Mastellos DC, Reis ES, Yancopoulou D, Hajishengallis G, Ricklin D, Lambris JD.

Immunobiology. 2016 Oct;221(10):1046-57. doi: 10.1016/j.imbio.2016.06.013. Epub 2016 Jun 16. Review.


New milestones ahead in complement-targeted therapy.

Ricklin D, Lambris JD.

Semin Immunol. 2016 Jun;28(3):208-22. doi: 10.1016/j.smim.2016.06.001. Epub 2016 Jun 16. Review.


Complement in disease: a defence system turning offensive.

Ricklin D, Reis ES, Lambris JD.

Nat Rev Nephrol. 2016 Jul;12(7):383-401. doi: 10.1038/nrneph.2016.70. Epub 2016 May 23. Review.


Properdin-Mediated C5a Production Enhances Stable Binding of Platelets to Granulocytes in Human Whole Blood.

Blatt AZ, Saggu G, Kulkarni KV, Cortes C, Thurman JM, Ricklin D, Lambris JD, Valenzuela JG, Ferreira VP.

J Immunol. 2016 Jun 1;196(11):4671-4680. doi: 10.4049/jimmunol.1600040. Epub 2016 Apr 25.


Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application.

Hajishengallis G, Hajishengallis E, Kajikawa T, Wang B, Yancopoulou D, Ricklin D, Lambris JD.

Semin Immunol. 2016 Jun;28(3):285-91. doi: 10.1016/j.smim.2016.03.006. Epub 2016 Mar 24. Review.


Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.

Forneris F, Wu J, Xue X, Ricklin D, Lin Z, Sfyroera G, Tzekou A, Volokhina E, Granneman JC, Hauhart R, Bertram P, Liszewski MK, Atkinson JP, Lambris JD, Gros P.

EMBO J. 2016 May 17;35(10):1133-49. doi: 10.15252/embj.201593673. Epub 2016 Mar 24.


Selectivity of C3-opsonin targeted complement inhibitors: A distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients.

Schmidt CQ, Harder MJ, Nichols EM, Hebecker M, Anliker M, Höchsmann B, Simmet T, Csincsi ÁI, Uzonyi B, Pappworth IY, Ricklin D, Lambris JD, Schrezenmeier H, Józsi M, Marchbank KJ.

Immunobiology. 2016 Apr;221(4):503-11. doi: 10.1016/j.imbio.2015.12.009. Epub 2016 Jan 6.


Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3.

Maekawa T, Briones RA, Resuello RR, Tuplano JV, Hajishengallis E, Kajikawa T, Koutsogiannaki S, Garcia CA, Ricklin D, Lambris JD, Hajishengallis G.

J Clin Periodontol. 2016 Mar;43(3):238-49. doi: 10.1111/jcpe.12507. Epub 2016 Mar 3.


Comparative Analysis of Novel Complement-Targeted Inhibitors, MiniFH, and the Natural Regulators Factor H and Factor H-like Protein 1 Reveal Functional Determinants of Complement Regulation.

Harder MJ, Anliker M, Höchsmann B, Simmet T, Huber-Lang M, Schrezenmeier H, Ricklin D, Lambris JD, Barlow PN, Schmidt CQ.

J Immunol. 2016 Jan 15;196(2):866-76. doi: 10.4049/jimmunol.1501919. Epub 2015 Dec 7.


Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40.

Wang J, Wang L, Xiang Y, Ricklin D, Lambris JD, Chen G.

Clin Immunol. 2016 Jan;162:37-44. doi: 10.1016/j.clim.2015.11.002. Epub 2015 Nov 6.


Attenuation of Staphylococcus aureus-Induced Bacteremia by Human Mini-Antibodies Targeting the Complement Inhibitory Protein Efb.

Georgoutsou-Spyridonos M, Ricklin D, Pratsinis H, Perivolioti E, Pirmettis I, Garcia BL, Geisbrecht BV, Foukas PG, Lambris JD, Mastellos DC, Sfyroera G.

J Immunol. 2015 Oct 15;195(8):3946-58. doi: 10.4049/jimmunol.1500966. Epub 2015 Sep 4.


Applying complement therapeutics to rare diseases.

Reis ES, Mastellos DC, Yancopoulou D, Risitano AM, Ricklin D, Lambris JD.

Clin Immunol. 2015 Dec;161(2):225-40. doi: 10.1016/j.clim.2015.08.009. Epub 2015 Sep 1. Review.


Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention.

Mastellos DC, Ricklin D, Hajishengallis E, Hajishengallis G, Lambris JD.

Mol Oral Microbiol. 2016 Feb;31(1):3-17. doi: 10.1111/omi.12129. Epub 2015 Oct 7. Review.


Contact activation of C3 enables tethering between activated platelets and polymorphonuclear leukocytes via CD11b/CD18.

Hamad OA, Mitroulis I, Fromell K, Kozarcanin H, Chavakis T, Ricklin D, Lambris JD, Ekdahl KN, Nilsson B.

Thromb Haemost. 2015 Nov 25;114(6):1207-17. doi: 10.1160/TH15-02-0162. Epub 2015 Aug 13.


Therapeutic control of complement activation at the level of the central component C3.

Ricklin D, Lambris JD.

Immunobiology. 2016 Jun;221(6):740-6. doi: 10.1016/j.imbio.2015.06.012. Epub 2015 Jun 10. Review.


Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria.

Lin Z, Schmidt CQ, Koutsogiannaki S, Ricci P, Risitano AM, Lambris JD, Ricklin D.

Blood. 2015 Aug 13;126(7):891-4. doi: 10.1182/blood-2015-02-625871. Epub 2015 Jun 16.


Compstatin analog Cp40 inhibits complement dysregulation in vitro in C3 glomerulopathy.

Zhang Y, Shao D, Ricklin D, Hilkin BM, Nester CM, Lambris JD, Smith RJ.

Immunobiology. 2015 Aug;220(8):993-8. doi: 10.1016/j.imbio.2015.04.001. Epub 2015 May 5.


Rare loss-of-function mutation in complement component C3 provides insight into molecular and pathophysiological determinants of complement activity.

Sfyroera G, Ricklin D, Reis ES, Chen H, Wu EL, Kaznessis YN, Ekdahl KN, Nilsson B, Lambris JD.

J Immunol. 2015 Apr 1;194(7):3305-16. doi: 10.4049/jimmunol.1402781. Epub 2015 Feb 23.


Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention.

Mastellos DC, Yancopoulou D, Kokkinos P, Huber-Lang M, Hajishengallis G, Biglarnia AR, Lupu F, Nilsson B, Risitano AM, Ricklin D, Lambris JD.

Eur J Clin Invest. 2015 Apr;45(4):423-40. doi: 10.1111/eci.12419. Epub 2015 Mar 9. Review.


Complement deficiency promotes cutaneous wound healing in mice.

Rafail S, Kourtzelis I, Foukas PG, Markiewski MM, DeAngelis RA, Guariento M, Ricklin D, Grice EA, Lambris JD.

J Immunol. 2015 Feb 1;194(3):1285-91. doi: 10.4049/jimmunol.1402354. Epub 2014 Dec 29.


Therapeutic C3 inhibitor Cp40 abrogates complement activation induced by modern hemodialysis filters.

Reis ES, DeAngelis RA, Chen H, Resuello RR, Ricklin D, Lambris JD.

Immunobiology. 2015 Apr;220(4):476-82. doi: 10.1016/j.imbio.2014.10.026. Epub 2014 Nov 3.


The extracellular adherence protein from Staphylococcus aureus inhibits the classical and lectin pathways of complement by blocking formation of the C3 proconvertase.

Woehl JL, Stapels DAC, Garcia BL, Ramyar KX, Keightley A, Ruyken M, Syriga M, Sfyroera G, Weber AB, Zolkiewski M, Ricklin D, Lambris JD, Rooijakkers SHM, Geisbrecht BV.

J Immunol. 2014 Dec 15;193(12):6161-6171. doi: 10.4049/jimmunol.1401600. Epub 2014 Nov 7.

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