Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies

Cancer Cell

Volumn 33, Issue 4, 2018, Pages 664-675.e4

  Yu, Xiaojie ^a   Chan, H T Claude ^a   Orr, Christian M ^a   Dadas, Osman ^a   Booth, Steven G ^a   Dahal, Lekh N ^a   Penfold, Christine A ^a   O'Brien, Lyn ^a,e   Mockridge, C Ian ^a   French, Ruth R ^a   Duriez, Patrick ^a   Douglas, Leon R ^a   Pearson, Arwen R ^b   Cragg, Mark S ^a,c   Tews, Ivo ^c   Glennie, Martin J ^a   White, Ann L ^a,d  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b UNIVERSITY OF HAMBURG   (Germany)

^c UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^d UCB PHARMA   (Belgium)

^e DEFENCE SCIENCE AND TECHNOLOGY LABORATORY   (United Kingdom)

Author keywords

agonist; antagonist; CD40; crystal structure; epitope; Fc receptors; immunotherapy; isotype; monoclonal antibody; TNFR

Indexed keywords

CD40 LIGAND MONOCLONAL ANTIBODY; CP 870893; DACETUZUMAB; EPITOPE; MONOCLONAL ANTIBODY CHILOB 7 4; UNCLASSIFIED DRUG; CD40 ANTIGEN; CD40 LIGAND; CROSS LINKING REAGENT; MONOCLONAL ANTIBODY; PROTEIN BINDING;

ADOPTIVE TRANSFER; AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANTIGEN SPECIFICITY; ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; BIOLOGICAL ACTIVITY; CD8+ T LYMPHOCYTE; CELL EXPANSION; COMPARATIVE STUDY; COMPLEMENTARITY DETERMINING REGION; CONTROLLED STUDY; DISULFIDE BOND; DRUG RECEPTOR BINDING; EPITOPE MAPPING; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IN VITRO STUDY; LYMPHOCYTE PROLIFERATION; MOUSE; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; SPLENIC B CELL; UPREGULATION; WESTERN BLOTTING; AGONISTS; ANTIBODY SPECIFICITY; CHEMISTRY; DRUG EFFECT; METABOLISM; MOLECULAR MODEL;

ANTIBODIES, MONOCLONAL; ANTIBODY SPECIFICITY; CD40 ANTIGENS; CD40 LIGAND; CROSS-LINKING REAGENTS; EPITOPES; HUMANS; MODELS, MOLECULAR; PROTEIN BINDING;

EID: 85042674460     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2018.02.009     Document Type: Article

References (51)

1. Ahonen, C., Manning, E., Erickson, L.D., O'Connor, B., Lind, E.F., Pullen, S.S., Kehry, M.R., Noelle, R.J., The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells. Nat. Immunol. 3 (2002), 451–456.
2. Allen, M.J., Guo, A., Martinez, T., Han, M., Flynn, G.C., Wypych, J., Liu, Y.D., Shen, W.D., Dillon, T.M., Vezina, C., Balland, A., Interchain disulfide bonding in human IgG2 antibodies probed by site-directed mutagenesis. Biochemistry 48 (2009), 3755–3766.
3. Barr, T.A., Heath, A.W., Functional activity of CD40 antibodies correlates to the position of binding relative to CD154. Immunology 102 (2001), 39–43.
4. Beatty, G.L., Chiorean, E.G., Fishman, M.P., Saboury, B., Teitelbaum, U.R., Sun, W., Huhn, R.D., Song, W., Li, D., Sharp, L.L., et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331 (2011), 1612–1616.
5. Beers, S.A., Glennie, M.J., White, A.L., Influence of immunoglobulin isotype on therapeutic antibody function. Blood 127 (2016), 1097–1101.
6. Bjorck, P., Braesch-Andersen, S., Paulie, S., Antibodies to distinct epitopes on the CD40 molecule co-operate in stimulation and can be used for the detection of soluble CD40. Immunology 83 (1994), 430–437.
7. Boross, P., Arandhara, V.L., Martin-Ramirez, J., Santiago-Raber, M.L., Carlucci, F., Flierman, R., van der Kaa, J., Breukel, C., Claassens, J.W., Camps, M., et al. The inhibiting Fc receptor for IgG, FcgammaRIIB, is a modifier of autoimmune susceptibility. J. Immunol. 187 (2011), 1304–1313.
8. Bulek, A.M., Madura, F., Fuller, A., Holland, C.J., Schauenburg, A.J., Sewell, A.K., Rizkallah, P.J., Cole, D.K., TCR/pMHC optimized protein crystallization screen. J. Immunol. Methods 382 (2012), 203–210.
9. Challa, A., Pound, J.D., Armitage, R.J., Gordon, J., Epitope-dependent synergism and antagonism between CD40 antibodies and soluble CD40 ligand for the regulation of CD23 expression and IgE synthesis in human B cells. Allergy 54 (1999), 576–583.
10. Chan, A.C., Carter, P.J., Therapeutic antibodies for autoimmunity and inflammation. Nat. Rev. Immunol. 10 (2010), 301–316.
11. Chan, F.K., Chun, H.J., Zheng, L., Siegel, R.M., Bui, K.L., Lenardo, M.J., A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288 (2000), 2351–2354.
12. Croft, M., Benedict, C.A., Ware, C.F., Clinical targeting of the TNF and TNFR superfamilies. Nat. Rev. Drug Discov. 12 (2013), 147–168.
13. Dahan, R., Barnhart, B.C., Li, F., Yamniuk, A.P., Korman, A.J., Ravetch, J.V., Therapeutic activity of agonistic, human anti-CD40 monoclonal antibodies requires selective fcgammar engagement. Cancer Cell 29 (2016), 820–831.
14. Dillon, T.M., Ricci, M.S., Vezina, C., Flynn, G.C., Liu, Y.D., Rehder, D.S., Plant, M., Henkle, B., Li, Y., Deechongkit, S., et al. Structural and functional characterization of disulfide isoforms of the human IgG2 subclass. J. Biol. Chem. 283 (2008), 16206–16215.
15. Ellmark, P., Ottosson, C., Borrebaeck, C.A., Malmborg Hager, A.C., Furebring, C., Modulation of the CD40-CD40 ligand interaction using human anti-CD40 single-chain antibody fragments obtained from the n-CoDeR phage display library. Immunology 106 (2002), 456–463.
16. Emsley, P., Lohkamp, B., Scott, W.G., Cowtan, K., Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66 (2010), 486–501.
17. Evans, P.R., Murshudov, G.N., How good are my data and what is the resolution?. Acta Crystallogr. D Biol. Crystallogr. 69 (2013), 1204–1214.
18. Gladue, R.P., Paradis, T., Cole, S.H., Donovan, C., Nelson, R., Alpert, R., Gardner, J., Natoli, E., Elliott, E., Shepard, R., Bedian, V., The CD40 agonist antibody CP-870,893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice. Cancer Immunol. Immunother. 60 (2011), 1009–1017.
19. Graves, J.D., Kordich, J.J., Huang, T.H., Piasecki, J., Bush, T.L., Sullivan, T., Foltz, I.N., Chang, W., Douangpanya, H., Dang, T., et al. Apo2L/TRAIL and the death receptor 5 agonist antibody AMG 655 cooperate to promote receptor clustering and antitumor activity. Cancer Cell 26 (2014), 177–189.
20. Grewal, I.S., Flavell, R.A., CD40 and CD154 in cell-mediated immunity. Annu. Rev. Immunol. 16 (1998), 111–135.
21. Malmborg Hager, A.C., Ellmark, P., Borrebaeck, C.A., Furebring, C., Affinity and epitope profiling of mouse anti-CD40 monoclonal antibodies. Scand. J. Immunol. 57 (2003), 517–524.
22. Haswell, L.E., Glennie, M.J., Al-Shamkhani, A., Analysis of the oligomeric requirement for signaling by CD40 using soluble multimeric forms of its ligand, CD154. Eur. J. Immunol. 31 (2001), 3094–3100.
23. Hussein, M., Berenson, J.R., Niesvizky, R., Munshi, N., Matous, J., Sobecks, R., Harrop, K., Drachman, J.G., Whiting, N., A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma. Haematologica 95 (2010), 845–848.
24. Johnson, P., Challis, R., Chowdhury, F., Gao, Y., Harvey, M., Geldart, T., Kerr, P., Chan, C., Smith, A., Steven, N., et al. Clinical and biological effects of an agonist anti-CD40 antibody: a Cancer Research UK phase I study. Clin. Cancer Res. 21 (2015), 1321–1328.
25. Kabsch, W., Xds. Acta Crystallogr. D Biol. Crystallogr. 66 (2010), 125–132.
26. Krissinel, E., Henrick, K., Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372 (2007), 774–797.
27. Li, F., Ravetch, J.V., Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333 (2011), 1030–1034.
28. Li, F., Ravetch, J.V., Apoptotic and antitumor activity of death receptor antibodies require inhibitory Fcgamma receptor engagement. Proc. Natl. Acad. Sci. USA 109 (2012), 10966–10971.
29. Luhder, F., Huang, Y., Dennehy, K.M., Guntermann, C., Muller, I., Winkler, E., Kerkau, T., Ikemizu, S., Davis, S.J., Hanke, T., Hunig, T., Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists. J. Exp. Med. 197 (2003), 955–966.
30. Martinez, T., Guo, A., Allen, M.J., Han, M., Pace, D., Jones, J., Gillespie, R., Ketchem, R.R., Zhang, Y., Balland, A., Disulfide connectivity of human immunoglobulin G2 structural isoforms. Biochemistry 47 (2008), 7496–7508.
31. McCoy, A.J., Grosse-Kunstleve, R.W., Adams, P.D., Winn, M.D., Storoni, L.C., Read, R.J., Phaser crystallographic software. J. Appl. Crystallogr. 40 (2007), 658–674.
32. Murshudov, G.N., Vagin, A.A., Dodson, E.J., Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53 (1997), 240–255.
33. Pound, J.D., Challa, A., Holder, M.J., Armitage, R.J., Dower, S.K., Fanslow, W.C., Kikutani, H., Paulie, S., Gregory, C.D., Gordon, J., Minimal cross-linking and epitope requirements for CD40-dependent suppression of apoptosis contrast with those for promotion of the cell cycle and homotypic adhesions in human B cells. Int. Immunol. 11 (1999), 11–20.
34. Remer, M., White, A., Glennie, M., Al-Shamkhani, A., Johnson, P., The use of anti-CD40 mAb in cancer. Curr. Top. Microbiol. Immunol. 405 (2017), 165–207.
35. Richman, L.P., Vonderheide, R.H., Role of crosslinking for agonistic CD40 monoclonal antibodies as immune therapy of cancer. Cancer Immunol. Res. 2 (2014), 19–26.
36. Schaer, D.A., Hirschhorn-Cymerman, D., Wolchok, J.D., Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy. J. Immunother. Cancer, 2, 2014, 7.
37. Sharma, P., Allison, J.P., Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell 161 (2015), 205–214.
38. Smulski, C.R., Beyrath, J., Decossas, M., Chekkat, N., Wolff, P., Estieu-Gionnet, K., Guichard, G., Speiser, D., Schneider, P., Fournel, S., Cysteine-rich domain 1 of CD40 mediates receptor self-assembly. J. Biol. Chem. 288 (2013), 10914–10922.
39. Tao, M.H., Morrison, S.L., Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. J. Immunol. 143 (1989), 2595–2601.
40. Vonderheide, R.H., Glennie, M.J., Agonistic CD40 antibodies and cancer therapy. Clin. Cancer Res. 19 (2013), 1035–1043.
41. Vonderheide, R.H., Flaherty, K.T., Khalil, M., Stumacher, M.S., Bajor, D.L., Hutnick, N.A., Sullivan, P., Mahany, J.J., Gallagher, M., Kramer, A., et al. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J. Clin. Oncol. 25 (2007), 876–883.
42. Werneburg, B.G., Zoog, S.J., Dang, T.T., Kehry, M.R., Crute, J.J., Molecular characterization of CD40 signaling intermediates. J. Biol. Chem. 276 (2001), 43334–43342.
43. White, A.L., Chan, H.T., Roghanian, A., French, R.R., Mockridge, C.I., Tutt, A.L., Dixon, S.V., Ajona, D., Verbeek, J.S., Al-Shamkhani, A., et al. Interaction with FcgammaRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody. J. Immunol. 187 (2011), 1754–1763.
44. White, A.L., Chan, H.T., French, R.R., Beers, S.A., Cragg, M.S., Johnson, P.W., Glennie, M.J., FcgammaRIotaIotaB controls the potency of agonistic anti-TNFR mAbs. Cancer Immunol. Immunother. 62 (2013), 941–948.
45. White, A.L., Dou, L., Chan, H.T., Field, V.L., Mockridge, C.I., Moss, K., Williams, E.L., Booth, S.G., French, R.R., Potter, E.A., et al. Fcgamma receptor dependency of agonistic CD40 antibody in lymphoma therapy can be overcome through antibody multimerization. J. Immunol. 193 (2014), 1828–1835.
46. White, A.L., Chan, H.T., French, R.R., Willoughby, J., Mockridge, C.I., Roghanian, A., Penfold, C.A., Booth, S.G., Dodhy, A., Polak, M.E., et al. Conformation of the human immunoglobulin G2 hinge imparts superagonistic properties to immunostimulatory anticancer antibodies. Cancer Cell 27 (2015), 138–148.
47. Wilson, N.S., Yang, B., Yang, A., Loeser, S., Marsters, S., Lawrence, D., Li, Y., Pitti, R., Totpal, K., Yee, S., et al. An Fcgamma receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell 19 (2011), 101–113.
48. Winn, M.D., Ballard, C.C., Cowtan, K.D., Dodson, E.J., Emsley, P., Evans, P.R., Keegan, R.M., Krissinel, E.B., Leslie, A.G., McCoy, A., et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D Biol. Crystallogr. 67 (2011), 235–242.
49. Wypych, J., Li, M., Guo, A., Zhang, Z., Martinez, T., Allen, M.J., Fodor, S., Kelner, D.N., Flynn, G.C., Liu, Y.D., et al. Human IgG2 antibodies display disulfide-mediated structural isoforms. J. Biol. Chem. 283 (2008), 16194–16205.
50. Xu, Y., Szalai, A.J., Zhou, T., Zinn, K.R., Chaudhuri, T.R., Li, X., Koopman, W.J., Kimberly, R.P., Fc gamma Rs modulate cytotoxicity of anti-Fas antibodies: implications for agonistic antibody-based therapeutics. J. Immunol. 171 (2003), 562–568.
51. Yamniuk, A.P., Suri, A., Krystek, S.R., Tamura, J., Ramamurthy, V., Kuhn, R., Carroll, K., Fleener, C., Ryseck, R., Cheng, L., et al. Functional antagonism of human CD40 achieved by targeting a unique species-specific epitope. J. Mol. Biol. 428 (2016), 2860–2879.