Comparing the efficacy and neuroinflammatory potential of three anti-abeta antibodies

Acta Neuropathologica

Volumn 130, Issue 5, 2015, Pages 699-711

  Fuller, James P ^a   Stavenhagen, Jeffrey B ^b   Christensen, Søren ^b   Kartberg, Fredrik ^b   Glennie, Martin J ^a   Teeling, Jessica L ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b H LUNDBECK A S   (Denmark)

Author keywords

Alzheimer s disease; Bapineuzumab; Crenezumab; Gantenerumab; Immunotherapy; Inflammation

Indexed keywords

AMYLOID BETA PROTEIN; BAPINEUZUMAB; CD11B ANTIGEN; CD68 ANTIGEN; CRENEZUMAB; EPITOPE; GANTENERUMAB; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G2A; INTERLEUKIN 1BETA; TUMOR NECROSIS FACTOR ALPHA; CD68 PROTEIN, MOUSE; DIFFERENTIATION ANTIGEN; IL1B PROTEIN, MOUSE; IMMUNOLOGIC FACTOR; LEUKOCYTE ANTIGEN; MONOCLONAL ANTIBODY; TUMOR NECROSIS FACTOR;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY PRODUCTION; ANTIGEN RETRIEVAL; ARTICLE; CELL ACTIVATION; COMPARATIVE EFFECTIVENESS; CONTROLLED STUDY; CYTOKINE RELEASE; DRUG EFFICACY; DRUG PROTEIN BINDING; EC50; EMBRYO; FEMALE; HIPPOCAMPUS; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOGLOBULIN BLOOD LEVEL; IMMUNOTHERAPY; IN VITRO STUDY; MACROPHAGE ACTIVATION; MICROGLIA; MOUSE; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN CROSS LINKING; PROTEIN EXPRESSION; TRANSGENIC MOUSE; UPREGULATION; ANIMAL; CELL LINE; COMPARATIVE STUDY; DRUG EFFECTS; GENETICS; IMMUNOLOGY; IMMUNOMODULATION; METABOLISM; PATHOLOGY; PHYSIOLOGY; PLAQUE, AMYLOID; PRECLINICAL STUDY;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD; ANTIGENS, CD11B; ANTIGENS, DIFFERENTIATION, MYELOMONOCYTIC; CELL LINE; DRUG EVALUATION, PRECLINICAL; FEMALE; HIPPOCAMPUS; HUMANS; IMMUNOLOGIC FACTORS; INTERLEUKIN-1BETA; MICE, TRANSGENIC; MICROGLIA; NEUROIMMUNOMODULATION; PLAQUE, AMYLOID; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84945195856     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-015-1484-2     Document Type: Article

References (33)

1. Adolfsson O, Pihlgren M, Toni N, Varisco Y, Buccarello AL, Antoniello K, Lohmann S, Piorkowska K, Gafner V, Atwal JK et al (2012) An effector-reduced anti-β-amyloid (Aβ) antibody with unique Aβ binding properties promotes neuroprotection and glial engulfment of Aβ. J Neurosci 32:9677–9689. doi:10.1523/jneurosci.4742-11.2012
2. Bard F, Cannon C, Barbour R, Burke RL, Games D, Grajeda H, Guido T, Hu K, Huang JP, Johnson-Wood K et al (2000) Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 6:916–919. doi:10.1038/78682
3. Bohrmann B, Baumann K, Benz J, Gerber F, Huber W, Knoflach F, Messer J, Oroszlan K, Rauchenberger R, Richter WF et al (2012) Gantenerumab: a novel human anti-A beta antibody demonstrates sustained cerebral amyloid-beta binding and elicits cell-mediated removal of human amyloid-beta. J Alzheimers Dis 28:49–69. doi:10.3233/jad-2011-110977
4. Bruhns P (2012) Properties of mouse and human IgG receptors and their contribution to disease models. Blood 119:5640–5649. doi:10.1182/blood-2012-01-380121
5. Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, Daeron M (2009) Specificity and affinity of human Fc gamma receptors and their polymorphic variants for human IgG subclasses. Blood 113:3716–3725. doi:10.1182/blood-2008-09-179754
6. Carty NC, Wilcock DM, Rosenthal A, Grimm J, Pons J, Ronan V, Gottschall PE, Gordon MN, Morgan D (2006) Intracranial administration of deglycosylated C-terminal-specific anti-Abeta antibody efficiently clears amyloid plaques without activating microglia in amyloid-depositing transgenic mice. J Neuroinflamm 3:11. doi:10.1186/1742-2094-3-11
7. Chan AC, Carter PJ (2010) Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 10:301–316. doi:10.1038/nri2761
8. Cribbs DH, Berchtold NC, Perreau V, Coleman PD, Rogers J, Tenner AJ, Cotman CW (2012) Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study. J Neuroinflamm 9:179. doi:10.1186/1742-2094-9-179
9. DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM (2001) Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease. P Natl Acad Sci USA 98:8850–8855. doi:10.1073/pnas.151261398
10. DeMattos Ronald B, Lu J, Tang Y, Racke Margaret M, DeLong Cindy A, Tzaferis John A, Hole Justin T, Forster Beth M, McDonnell Peter C, Liu F et al (2012) A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer’s disease mice. Neuron 76:908–920. doi:10.1016/j.neuron.2012.10.029
11. Dodart JC, Bales KR, Gannon KS, Greene SJ, DeMattos RB, Mathis C, DeLong CA, Wu S, Wu X, Holtzman DM et al (2002) Immunization reverses memory deficits without reducing brain A beta burden in Alzheimer’s disease model. Nat Neurosci 5:452–457. doi:10.1038/nn842
12. Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS et al (2014) Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 370:311–321. doi:10.1056/NEJMoa1312889
13. Freeman GB, Brown TP, Wallace K, Bales KR (2012) Chronic administration of an aglycosylated murine antibody of ponezumab does not worsen microhemorrhages in aged Tg2576 mice. Curr Alzheimer Res 9:1059–1068
14. Fuller JP, Stavenhagen JB, Teeling JL (2014) New roles for Fc receptors in neurodegeneration—the impact on immunotherapy for Alzheimer’s Disease. Front Neurosci 8:235. doi:10.3389/fnins.2014.00235
15. Hardy J, Selkoe DJ (2002) Medicine—the amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356
16. Lunnon K, Teeling JL, Tutt AL, Cragg MS, Glennie MJ, Perry VH (2011) Systemic inflammation modulates Fc receptor expression on microglia during chronic neurodegeneration. J Immunol 186:7215–7224. doi:10.4049/jimmunol.0903833
17. Miles LA, Crespi GAN, Doughty L, Parker MW (2013) Bapineuzumab captures the N-terminus of the Alzheimer’s disease amyloid-beta peptide in a helical conformation. Sci Rep 3:1302. doi:10.1038/srep01302
18. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969
19. Nimmerjahn F, Ravetch JV (2008) Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 8:34–47. doi:10.1038/nri2206
20. Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S et al (2003) Subacute meningoencephalitis in a subset of patients with AD after A beta 42 immunization. Neurology 61:46–54
21. Peress NS, Fleit HB, Perillo E, Kuljis R, Pezzullo C (1993) Identifcation of Fc gamma RI, II and III on normal human brain ramified microglia in senile plaques in Alzheimer’s Disease. J Neuroimmunol 48:71–80. doi:10.1016/0165-5728(93)90060-c
22. Rinne JO, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, Mathis CA, Blennow K, Barakos J, Okello AA et al (2010) (11)C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 9:363–372. doi:10.1016/s1474-4422(10)70043-0
23. Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S et al (2014) Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 370:322–333. doi:10.1056/NEJMoa1304839
24. Salloway SP, Black R, Sperling R, Fox N, Gilman S, Schenk D, Grundman M (2010) A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease reply. Neurology 74:2026–2027
25. Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang JP, Johnson-Wood K, Khan K et al (1999) Immunization with amyloid-beta attenuates Alzheimer disease-like pathology in the PDAPP mouse. Nature 400:173–177. doi:10.1038/22124
26. Sudduth TL, Greenstein A, Wilcock DM (2013) Intracranial injection of Gammagard, a human IVIg, modulates the inflammatory response of the brain and lowers A beta in APP/PS1 mice along a different time course than anti-A beta antibodies. J Neurosci 33:9684–9692. doi:10.1523/jneurosci.1220-13.2013
27. Teeling JL, Carare RO, Glennie MJ, Perry VH (2012) Intracerebral immune complex formation induces inflammation in the brain that depends on Fc receptor interaction. Acta Neuropathol 124:479–490. doi:10.1007/s00401-012-0995-3
28. Watt AD, Crespi GAN, Down RA, Ascher DB, Gunn A, Perez KA, McLean CA, Villemagne VL, Parker MW, Barnham KJ et al (2014) Do current therapeutic anti-A beta antibodies for Alzheimer’s disease engage the target? Acta Neuropathol 127:803–810. doi:10.1007/s00401-014-1290-2
29. Wilcock DM, Alamed J, Gottschall PE, Grimm J, Rosenthal A, Pons J, Ronan V, Symmonds K, Gordon MN, Morgan D (2006) Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice. J Neurosci Off J Soc Neurosci 26:5340–5346. doi:10.1523/JNEUROSCI.0695-06.2006
30. Wilcock DM, DiCarlo G, Henderson D, Jackson J, Clarke K, Ugen KE, Gordon MN, Morgan D (2003) Intracranially administered anti-Abeta antibodies reduce beta-amyloid deposition by mechanisms both independent of and associated with microglial activation. J Neurosci Off J Soc Neurosci 23:3745–3751
31. Wilcock DM, Munireddy SK, Rosenthal A, Ugen KE, Gordon MN, Morgan D (2004) Microglial activation facilitates Abeta plaque removal following intracranial anti-Abeta antibody administration. Neurobiol Dis 15:11–20
32. Wilcock DM, Rojiani A, Rosenthal A, Levkowitz G, Subbarao S, Alamed J, Wilson D, Wilson N, Freeman MJ, Gordon MN et al (2004) Passive amyloid immunotherapy clears amyloid and transiently activates microglia in a transgenic mouse model of amyloid deposition. J Neurosci Off J Soc Neurosci 24:6144–6151. doi:10.1523/JNEUROSCI.1090-04.2004
33. Wilcock DM, Zhao Q, Morgan D, Gordon MN, Everhart A, Wilson JG, Lee JE, Colton CA (2011) Diverse inflammatory responses in transgenic mouse models of AD and the effect of immunotherapy on these responses. ASN Neuro 3(5):249-258. doi 10.1042/AN20110018