Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env protein

mAbs

Volumn 7, Issue 1, 2015, Pages 265-275

  Curtin, Franҫois ^a,b   Perron, Hervé ^a   Kromminga, Arno ^c,d   Porchet, Hervé ^a,e   Lang, Alois B ^a  

^a GENEURO SA   (Switzerland)

^b UNIVERSITY OF GENEVA   (Switzerland)

^c UNIVERSITY OF KIEL   (Germany)

^d IPM   (Germany)

^e UNIVERSITY OF PRETORIA   (South Africa)

Author keywords

Drug safety; HERV W; Human endogenous retrovirus; Monoclonal antibody; MSRV; Multiple sclerosis; Neurotoxicity; Syncytin; Toxicology

Indexed keywords

FREUND ADJUVANT; IMMUNOGLOBULIN G1 ANTIBODY; IMMUNOGLOBULIN G4; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY GNBAC1; MONOCLONAL ANTIBODY GNBAC1 IGG1; MONOCLONAL ANTIBODY GNBAC1 IGG4; PLACEBO; RITUXIMAB; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN; GNBAC1 MONOCLONAL ANTIBODY; IMMUNOGLOBULIN G;

ADJUVANT THERAPY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; BURN; CLINICAL ARTICLE; COMPARATIVE EFFECTIVENESS; COMPLEMENT ACTIVATION; COMPLEMENT DEPENDENT CYTOTOXICITY; COMPUTER MODEL; CONTROLLED STUDY; CROSS REACTION; CYSTITIS; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CYTOTOXICITY; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DRUG SAFETY; DRUG SCREENING; DRUG SPECIFICITY; DRUG SURVEILLANCE PROGRAM; DRUG TARGETING; DRUG TOLERABILITY; ECG ABNORMALITY; ELIMINATION HALF-LIFE; EXPERIMENTAL ALLERGIC ENCEPHALITIS; FATIGUE; FEMALE; FLOW CYTOMETRY; FLU LIKE SYNDROME; GAIT DISORDER; HEMATOMA; HUMAN; HUMAN CELL; HUMAN TISSUE; HUMORAL IMMUNITY; HYPERGLYCEMIA; IMMUNOGENICITY; IN VITRO STUDY; IN VIVO STUDY; LEUKOCYTURIA; LONG TERM CARE; MALE; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; MOUSE; MULTIPLE SCLEROSIS; MULTIPLE SCLEROSIS ASSOCIATED RETROVIRUS; MUSCLE SPASM; NATURAL KILLER CELL; NAUSEA; NONHUMAN; OPEN STUDY; OROPHARYNX PAIN; PANCREATITIS; PATHOPHYSIOLOGY; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PROTEIN EXPRESSION; PROTEIN TARGETING; PROTEINURIA; REPEATED DRUG DOSE; RETROVIRUS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RHINITIS; RHINOPHARYNGITIS; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE; SINUS BRADYCARDIA; SITE DIRECTED MUTAGENESIS; THORAX PAIN; TOXICOKINETICS; TREATMENT RESPONSE; VOLUME OF DISTRIBUTION; ANIMAL; ANTIBODY SPECIFICITY; CLINICAL TRIAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; ENDOGENOUS RETROVIRUS; HEK293 CELL LINE; IMMUNOLOGY; PATHOLOGY; RANDOMIZED CONTROLLED TRIAL;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIBODY SPECIFICITY; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; ENDOGENOUS RETROVIRUSES; FEMALE; GENE PRODUCTS, ENV; HEK293 CELLS; HUMANS; IMMUNOGLOBULIN G; MALE; MICE; MULTIPLE SCLEROSIS;

EID: 84921343959     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/19420862.2014.985021     Document Type: Article

References (39)

1. McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 2007; 8:913-9; PMID:17712344; http://dx.doi.org/10.1038/ni1507
2. Fontoura P. Monoclonal antibody therapy in multiple sclerosis. mAbs 2010; 2:670-81; PMID:21124072; http://dx.doi.org/10.4161/mabs.2.6.13270
3. Hoepner R, Faissner S, Salmen A, Gold R, Chan A. Efficacy and side effects of natalizumab therapy in patients with multiple sclerosis. J Cent Nerv Syst Dis 2014; 6:41-9; PMID:24855407; http://dx.doi.org/10.4137/JCNSD.S14049
4. Coles AJ. Alemtuzumab therapy for multiple sclerosis. Neurotherapeutics 2013; 10:29-33; PMID:23184314; http://dx.doi.org/10.1007/s13311-012-0159-0
5. Curtin F, Hartung HP. Novel therapeutic options for multiple sclerosis. Expert Rev Clin Pharmacol 2014; 7:91-104; PMID:24325127; http://dx.doi.org/10.1586/17512433.2014.865517
6. Perron H, Garson JA, Bedin F, Beseme F, Paranhos- Baccala G, Komurian-Pradel F, Mallet F, Tuke PW, Voisset C, Blond JL, et al. Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. The collaborative research group on multiple sclerosis. Proc Natl Acad Sci U S A 1997; 94:7583-8; PMID:9207135; http://dx.doi.org/10.1073/pnas.94.14.7583
7. Sotgiu S, Mameli G, Serra C, Zarbo IR, Arru G, Dolei A. Multiple sclerosis-associated retrovirus and progressive disability of multiple sclerosis. Mult Scler 2010; 16:1248-51; PMID:20685761; http://dx.doi.org/10.1177/1352458510376956
8. Mameli G, Astone V, Arru G, Marconi S, Lovato L, Serra C, Sotgiu S, Bonetti B, Dolei A. Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirusHERV-W endogenous retrovirus, but not Human herpesvirus 6. J Gen Virol 2007; 88:264-74; PMID:17170460; http://dx. doi.org/10.1099/vir.0.81890-0
9. Rolland, A., Jouvin-Marche E, Saresella M, Ferrante P, Cavaretta R, Créange A, Marche P, Perron H. Correlation between disease severity and in vitro cytokine production mediated by MSRV (multiple sclerosis associated retroviral element) envelope protein in patients with multiple sclerosis. J Neuroimmunol 2005; 160:195-203; PMID:15710473; http://dx.doi.org/10.1016/j.jneuroim.2004.10.019
10. Rolland A, Jouvin-Marche E, Viret C, Faure M, Perron H, Marche PN. The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14TLR4 and promotes Th1- like responses. J Immunol 2006; 176:7636-44; PMID:16751411; http://dx.doi.org/10.4049/ jimmunol.176.12.7636
11. Kremer D1, Schichel T, Förster M, Tzekova N, Bernard C, van der Valk P, van Horssen J, Hartung HP, Perron H, Küry P. Human endogenous retrovirus type W envelope protein inhibits oligodendroglial precursor cell differentiation. Ann Neurol 2013; 74:721-32; PMID:23836485; http://dx.doi.org/10.1002/ana.23970
12. Ruprecht K, Gronen F, Sauter M, Best B, Rieckmann P, Mueller-Lantzsch N. Lack of immune responses against multiple sclerosis-associated retrovirushuman endogenous retrovirus W in patients with multiple sclerosis. J Neurovirol 2008; 14:143-51; PMID:18444086; http://dx.doi. org/10.1080/13550280801958922
13. Voisset C, Blancher A, Perron H, Mandrand B, Mallet F, Paranhos-Baccala G. Phylogeny of a novel family of human endogenous retrovirus sequences, HERV-W, in humans and other primates. AIDS Res Hum Retroviruses 1999; 15:1529-33; PMID:10580403; http://dx. doi.org/10.1089/088922299309810
14. Belshaw R, Pereira V, Katzourakis A, Talbot G, Paces J, Burt A, Tristem M. Long-term reinfection of the human genome by endogenous retroviruses. Proc Natl Acad Sci U S A 2004; 101:4894-9; PMID:15044706; http://dx.doi.org/10.1073/pnas.0307800101
15. Weiss RA. The discovery of endogenous retroviruses. Retrovirology 2006; 3:67; PMID:17018135; http://dx. doi.org/10.1186/1742-4690-3-67
16. Perron H, Germi R, Bernard C, Garcia-Montojo M, Deluen C, Farinelli L, Faucard R, Veas F, Stefas I, Fabriek BO, et al. Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Mult Scler 2012; 18:1721-36; PMID:22457345; http://dx.doi. org/10.1177/1352458512441381
17. Alliel PM, Perin JP, Goudou D, Bitoun M, Robert B, Rieger F. The HERV-W7q family in the human genome. Potential for protein expression and gene regulation. Cell Mol Biol (Noisy-le-Grand) 2002; 48:213-17; PMID:11990458
18. Blond JL, Beseme F, Duret L, Bouton O, Bedin F, Perron H, Mandrand B, Mallet F. Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. J Virol 1999; 73:1175-85; PMID:9882319
19. Voisset C, Bouton O, Bedin F, Duret L, Mandrand B, Mallet F, Paranhos-Baccala G. Chromosomal distribution and coding capacity of the human endogenous retrovirus HERV-W family. AIDS Res Hum Retroviruses 2000; 16:731-40; PMID:10826480; http://dx.doi.org/10.1089/088922200308738
20. Perron H, Rolland A, Marche P, Jouvin-Marche E, Inventors; Biomerieux, INSERM Assignees. Composition for treating pathology associated with MSRV/ HERV-W. US patent US7666420B2 2010 Feb 23
21. Trejbalová K, Blazková J, Matousková M, Kucerová D, Pecnová L, Vernerová Z, Herácek J, Hirsch I, Hejnar J. Epigenetic regulation of transcription and splicing of syncytins, fusogenic glycoproteins of retroviral origin. Nucleic Acids Res 2011; 39:8728-39; PMID:21771862; http://dx.doi.org/10.1093/nar/gkr562
22. Perron H, Dougier-Reynaud HL, Lomparski C, Popa I, Firouzi R, Bertrand JB, Marusic S, Portoukalian J, Jouvin-Marche E, Villiers CL, et al. Human endogenous retrovirus protein activates innate immunity and promotes experimental allergic encephalomyelitis in mice. PLoS One 2013; 8:e80128; PMID:24324591; http://dx.doi.org/10.1371/journal.pone.0080128
23. Curtin F, Lang AB, Perron H, Laumonier M, Vidal V, Porchet HC, Hartung HP. GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus: a first-in-humans randomized clinical study. Clin Ther 2012; 34:2268-78; PMID:23200102; http://dx.doi. org/10.1016/j.clinthera.2012.11.006
24. Derfuss T, Curtin F, Lang AB, Perron H, Kappos L, Lalive P. GNbAC1, a humanised monoclonal antibody against the multiple sclerosis associated retrovirus envelope protein is well tolerated in patients with multiple sclerosis. Poster session presented at: 66th Annual Meeting of the American Academy of Neurology, 26 April - 3 May 2014, Philadelphia, PA.
25. Derfuss T, Curtin F, Guebelin C, Bridel C, Rasenack M, Matthey A, Du Pasquier R, Schluep M, Desmeules J, Lang AB, et al. A phase IIa randomized clinical study of GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis associated endogenous retrovirus in multiple sclerosis patients. Multiple Scler 2014 Nov 12; pii: 1352458514554052 [Epub ahead of print]
26. Marchi E, Kanapin A, Magiorkinis G, Belshaw R. Unfixed endogenous retroviral insertions in the human population. J Virol 2014; 88:9529-37; In press; PMID:24920817; http://dx.doi.org/10.1128/JVI.00919-14
27. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Preclinical safety evaluation of biotechnology- derived pharmaceuticals S6(R1). June 2011; http:// www.ich.orgfileadminPublic-Web-SiteICH-Products GuidelinesSafetyS6-R1Step4S6-R1-Guideline.pdf"〉 http:www.ich.orgfileadminPublic-Web-SiteICH- ProductsGuidelinesSafetyS6-R1Step4S6-R1-Guideline. pdf
28. Mameli G, Poddighe L, Mei A, Uleri E, Sotgiu S, Serra C, Manetti R, Dolei A. Expression and activation by Epstein Barr virus of human endogenous retroviruses- W in blood cells and astrocytes: inference for multiple sclerosis. PLoS One 2012; 7:e44991; PMID:23028727; http://dx.doi.org/10.1371/journal. pone.0044991
29. Brennan FR, Morton LD, Spindeldreher S, Kiessling A, Allenspach R, Hey A, Muller PY, Frings W, Sims J. Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies. MAbs 2010; 2:233-55; PMID:20421713
30. Wang W1, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2008 Nov; 84(5):548-58; PMID:18784655; http://dx.doi.org/10.1038/clpt.2008.170
31. Kaschka WP, Theilkaes L, Eickhoff K, Skvaril F. Disproportionate elevation of the immunoglobulin G1 concentration in cerebrospinal fluids of patients with multiple sclerosis. Infect Immun 1979 Dec; 26(3):933-41; PMID:528058
32. Petereit HF, Rubbert-Roth A. Rituximab levels in cerebrospinal fluid of patients with neurological autoimmune disorders. Mult Scler 2009 Feb; 15(2):189-92; PMID:18971221; http://dx.doi.org/10.1177/1352458508098268
33. Tran J, Palaparthy R, Zhao J, Brosofsky K, Ray S, Rana J, Cadavid D. Safety, tolerability and pharmacokinetics of the anti-lingo-1 monoclonal antibody BIIB033 in healthy volunteers and subjects with multiple sclerosis. Poster session presented at: 64th Annual Meeting of the American Academy of Neurology, 22-27 April 2012, New Orleans, LA.
34. Mould DR, Green B. Pharmacokinetics and pharmacodynamics of monoclonal antibodies: concepts and lessons for drug development. BioDrugs 2010 Feb 1; 24 (1):23-39; PMID:20055530; http://dx.doi.org/ 10.2165/11530560-000000000-00000
35. Mameli G, Serra C, Astone V, Castellazzi M, Poddighe L, Fainardi E, Neri W, Granieri E, Dolei A. Inhibition of multiple-sclerosis-associated retrovirus as biomarker of interferon therapy. J Neurovirol 2008; 14:73-77; PMID:18300077; http://dx.doi.org/10.1080/ 13550280701801107
36. Arru G, Leoni S, Pugliatti M, Mei A, Serra C, Delogu LG, Manetti R, Dolei A, Sotgiu S, Mameli G. Natalizumab inhibits the expression of human endogenous retroviruses of the W family in multiple sclerosis patients: a longitudinal cohort study. Mult Scler 2014; 20:174-182; PMID:23877972; http://dx.doi.org/10.1177/1352458513494957
37. Riminton DS, Hartung HP, Reddel SW. Managing the risks of immunosuppression. Curr Opin Neurol 2011; 24:217-23; PMID:21519254; http://dx.doi.org/ 10.1097/WCO.0b013e328346d47d
38. Stefas E, Rucheton M, Graafland H, Moynier M, Sompeyrac C, Bahraoui EM, Veas F. Human plasmatic apolipoprotein H binds human immunodeficiency virus type 1 and type 2 proteins. AIDS Res Hum Retroviruses 1997; 13:97-104; PMID:8989432; http://dx. doi.org/10.1089/aid.1997.13.97
39. Stefas I, Rucheton M, D'Angeac AD, Morel-Baccard C, Seigneurin JM, Zarski JP, Martin M, Cerutti M, Bossy JP, Missé D, et al. Hepatitis B virus Dane particles bind to human plasma apolipoprotein H. Hepatology 2001; 33:207-17; PMID:11124838; http://dx. doi.org/10.1053/jhep.2001.20531