Highly reduced binding to high and low affinity mouse Fc gamma receptors by L234A/L235A and N297A Fc mutations engineered into mouse IgG2a

Molecular Immunology

Volumn 63, Issue 2, 2015, Pages 456-463

  Arduin, E ^a   Arora, S ^a   Bamert, P R ^a   Kuiper, T ^a   Popp, S ^a   Geisse, S ^a   Grau, R ^a   Calzascia, T ^a   Zenke, G ^a   Kovarik, J ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Complement; Fc silencing mutations; Mouse Fc Rs binding; Mouse IgG2a

Indexed keywords

COMPLEMENT COMPONENT C1Q; FC RECEPTOR; IMMUNOGLOBULIN G2A; IMMUNOGLOBULIN G; MUTANT PROTEIN; OX40 LIGAND; PROTEIN BINDING; RECOMBINANT PROTEIN;

ANIMAL CELL; ANTIGEN BINDING; ARTICLE; BINDING AFFINITY; BINDING ASSAY; CHO CELL LINE; CONTROLLED STUDY; FLOW CYTOMETRY; GENE MUTATION; GENE SILENCING; MACROPHAGE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; RECEPTOR BINDING; AMINO ACID SEQUENCE; ANIMAL; CELL LINE; CHEMISTRY; GENETIC ENGINEERING; GENETICS; HUMAN; METABOLISM; MOLECULAR GENETICS; MUTATION; SEQUENCE ALIGNMENT;

AMINO ACID SEQUENCE; ANIMALS; CELL LINE; COMPLEMENT C1Q; FLOW CYTOMETRY; GENETIC ENGINEERING; HUMANS; IMMUNOGLOBULIN G; MACROPHAGES; MICE; MOLECULAR SEQUENCE DATA; MUTANT PROTEINS; MUTATION; OX40 LIGAND; PROTEIN BINDING; RECEPTORS, IGG; RECOMBINANT PROTEINS; SEQUENCE ALIGNMENT;

EID: 84912010283     PISSN: 01615890     EISSN: 18729142     Source Type: Journal    
DOI: 10.1016/j.molimm.2014.09.017     Document Type: Article

References (24)

1. Arnold J.N., Wormald M.R., Sim R.B., Rudd P.M., Dwek R.A. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu. Rev. Immunol. 2007, 25:21-50.
2. Bruhns P. Properties of mouse and human IgG receptors and their contribution to disease models. Blood 2012, 119:5640-5649.
3. Carter P.J. Potent antibody therapeutics by design. Nat. Rev. Immunol. 2006, 6:343-357.
4. Chao D.T., Ma X., Li O., Park H., Law D. Functional characterization of N297A, a murine surrogate for low-Fc binding anti-human CD3 antibodies. Immunol. Invest. 2009, 38(1):76-92.
5. Cho M.S., Yee H., Brown C., Mei B., Mirenda C., Chan S. Versatile expression system for rapid and stable production of recombinant proteins. Biotechnol. Prog. 2003, 19:229-232.
6. Duncan A.R., Winter G. The binding site for C1q on IgG. Nature 1988, 332:738-740.
7. Gadjeva M.G., Rouseva M.M., Zlatarova A.S., Reid K.B., Kishore U., Kojouharova M.S. Interaction of human C1q with IgG and IgM: revisited. Biochemistry 2008, 47:13093-13102.
8. Geisse S., Fux C. Recombinant protein production by transient gene transfer into Mammalian cells. Methods Enzymol. 2009, 463:223-238.
9. Hessell A.J., Hangartner L., Hunter M., Havenith C.E., Beurskens F.J., Bakker J.M., Lanigan C.M., Landucci G., Forthal D.N., Parren P.W., Marx P.A., Burton D.R. Fc receptor but not complement binding is important in antibody protection against HIV. Nature 2007, 449:101-104.
10. Hezareh M., Hessell A.J., Jensen R.C., van de Winkel J.G., Parren P.W. Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. J. Virol. 2001, 75:12161-12168.
11. Idusogie E.E., Presta L.G., Gazzano-Santoro H., Totpal K., Wong P.Y., Ultsch M., Meng Y.G., Mulkerrin M.G. Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc. J. Immunol. 2000, 164(8):4178-4184.
12. Joshi T., Ganesan L.P., Cao X., Tridandapani S. Molecular analysis of expression and function of hFcgammaRIIbl and b2 isoforms in myeloid cells. Mol. Immunol. 2006, 43:839-850.
13. Leabman M.K., Meng Y.G., Kelley R.F., DeForge L.E., Cowan K.J., Iyer S. Effects of altered FcgammaR binding on antibody pharmacokinetics in cynomolgus monkeys. MAbs 2013, 5:896-903.
14. Lux A., Nimmerjahn F. Of mice and men: the need for humanized mouse models to study human IgG activity in vivo. J. Clin. Immunol. 2013, 33(Suppl. 1):S4L S8.
15. Mancardi D.A., Iannascoli B., Hoos S., England P., Daeron M., Bruhns P. FcgammaRIV is a mouse IgE receptor that resembles macrophage FcepsilonRI in humans and promotes IgE-induced lung inflammation. J. Clin. Invest. 2008, 118:3738-3750.
16. Morgan A., Jones N.D., Nesbitt A.M., Chaplin L., Bodmer M.W., Emtage J.S. The N-terminal end of the CH2 domain of chimeric human IgG1 anti-HLA-DR is necessary for C1q, Fc gamma RI and Fc gamma RIII binding. Immunology 1995, 86:319-324.
17. Nimmerjahn F., Lux A., Albert H., Woigk M., Lehmann C., Dudziak D., Smith P., Ravetch J.V. FcgammaRIV deletion reveals its central role for IgG2a and IgG2b activity in vivo. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:19396-19401.
18. Nimmerjahn F., Ravetch J.V. Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 2005, 310:1510-1512.
19. Presta L.G. Engineering of therapeutic antibodies to minimize immunogenicity and optimize function. Adv. Drug Deliv. Rev. 2006, 58:640-656.
20. Sears D.W., Osman N., Tate B., McKenzie I.F., Hogarth P.M. Molecular cloning and expression of the mouse high affinity Fc receptor for IgG. J. Immunol. 1990, 144:371-378.
21. Shields R.L., Namenuk A.K., Hong K., Meng Y.G., Rae J., Briggs J., Xie D., Lai J., Stadlen A., Li B., Fox J.A., Presta L.G. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J. Biol. Chem. 2001, 276(9):6591-6604.
22. Strohl W.R. Optimization of Fc-mediated effector functions of monoclonal antibodies. Curr. Opin. Biotechnol. 2009, 20(6):685-691.
23. Wines B.D., Powell M.S., Parren P.W., Barnes N., Hogarth P.M. The IgG Fc contains distinct Fc receptor (FcR) binding sites: the leukocyte receptors Fc gamma RI and Fc gamma RIIa bind to a region in the Fc distinct from that recognized by neonatal FcR and protein A. J. Immunol. 2000, 164:5313-5318.
24. Xu D., Alegre M.L., Varga S.S., Rothermel A.L., Collins A.M., Pulito V.L., Hanna L.S., Dolan K.P., Parren P.W., Bluestone J.A., Jolliffe L.K., Zivin R.A. In vitro characterization of five humanized OKT3 effector function variant antibodies. Cell. Immunol. 2000, 200:16-26.