Antibodies to Costimulatory Receptor 4-1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8 T Cell Effector Function

Immunity

Volumn 49, Issue 5, 2018, Pages 958-970.e7

  Buchan, Sarah L ^a   Dou, Lang ^a   Remer, Marcus ^a   Booth, Steven G ^a   Dunn, Stuart N ^a   Lai, Chester ^a,b   Semmrich, Monika ^c   Teige, Ingrid ^c   Mårtensson, Linda ^c   Penfold, Christine A ^a   Chan, H T Claude ^a   Willoughby, Jane E ^a   Mockridge, C Ian ^a   Dahal, Lekh N ^a   Cleary, Kirstie L S ^a   James, Sonya ^a   Rogel, Anne ^a   Kannisto, Päivi ^d   Jernetz, Mats ^d   Williams, Emily L ^a   Healy, Eugene ^a,b   Verbeek, J Sjef ^e   Johnson, Peter W M ^a   Frendéus, Björn ^c   Cragg, Mark S ^a   Glennie, Martin J ^a   Gray, Juliet C ^a   Al Shamkhani, Aymen ^a   Beers, Stephen A ^a   more..

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST   (United Kingdom)

^c BioInvent International AB   (Sweden)

^d LUND UNIVERSITY HOSPITAL   (Sweden)

^e LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

4 1BB; agonism; cancer; combination; depletion; immunotherapy; PD 1; TNFR; Treg cell; tumor

Indexed keywords

FC RECEPTOR; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G2A; MONOCLONAL ANTIBODY; PROGRAMMED DEATH 1 RECEPTOR; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 9; IMMUNOGLOBULIN G;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY ENGINEERING; ARTICLE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; EFFECTOR CELL; HUMAN; HUMAN CELL; IN VIVO STUDY; LYMPHOCYTE FUNCTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T CELL DEPLETION; TUMOR IMMUNITY; TUMOR REJECTION; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECT; GENE EXPRESSION; GENETICS; IMMUNOLOGY; IMMUNOMODULATION; KNOCKOUT MOUSE; METABOLISM; NEOPLASM; TUMOR ASSOCIATED LEUKOCYTE;

ANIMALS; ANTIBODIES, MONOCLONAL; CD8-POSITIVE T-LYMPHOCYTES; GENE EXPRESSION; HUMANS; IMMUNOGLOBULIN G; IMMUNOMODULATION; LYMPHOCYTES, TUMOR-INFILTRATING; MICE; MICE, KNOCKOUT; NEOPLASMS; T-LYMPHOCYTES, REGULATORY; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 9;

EID: 85056674401     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2018.09.014     Document Type: Article

References (53)

1. Arce Vargas, F., Furness, A.J.S., Solomon, I., Joshi, K., Mekkaoui, L., Lesko, M.H., Miranda Rota, E., Dahan, R., Georgiou, A., Sledzinska, A., et al. Melanoma TRACERx Consortium Renal TRACERx Consortium, Lung TRACERx Consortium. Fc-optimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors. Immunity 46 (2017), 577–586.
2. Arce Vargas, F., Furness, A.J.S., Litchfield, K., Joshi, K., Rosenthal, R., Ghorani, E., Solomon, I., Lesko, M.H., Ruef, N., Roddie, C., et al. TRACERx Melanoma TRACERx Renal, TRACERx Lung consortia. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies. Cancer Cell 33 (2018), 649–663.e4.
3. 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.
4. Beers, S.A., Chan, C.H., James, S., French, R.R., Attfield, K.E., Brennan, C.M., Ahuja, A., Shlomchik, M.J., Cragg, M.S., Glennie, M.J., Type II (tositumomab) anti-CD20 monoclonal antibody out performs type I (rituximab-like) reagents in B-cell depletion regardless of complement activation. Blood 112 (2008), 4170–4177.
5. Beers, S.A., French, R.R., Chan, H.T., Lim, S.H., Jarrett, T.C., Vidal, R.M., Wijayaweera, S.S., Dixon, S.V., Kim, H., Cox, K.L., et al. Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection. Blood 115 (2010), 5191–5201.
6. Brahmer, J.R., Tykodi, S.S., Chow, L.Q., Hwu, W.J., Topalian, S.L., Hwu, P., Drake, C.G., Camacho, L.H., Kauh, J., Odunsi, K., et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366 (2012), 2455–2465.
7. Buchan, S.L., Al-Shamkhani, A., Distinct motifs in the intracellular domain of human CD30 differentially activate canonical and alternative transcription factor NF-κB signaling. PLoS ONE, 7, 2012, e45244.
8. + T-cell-driven antitumor immunity. Clin. Cancer Res. 24 (2018), 2383–2394.
9. Bulliard, Y., Jolicoeur, R., Windman, M., Rue, S.M., Ettenberg, S., Knee, D.A., Wilson, N.S., Dranoff, G., Brogdon, J.L., Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J. Exp. Med. 210 (2013), 1685–1693.
10. Curran, M.A., Allison, J.P., Tumor vaccines expressing flt3 ligand synergize with ctla-4 blockade to reject preimplanted tumors. Cancer Res. 69 (2009), 7747–7755.
11. Curran, M.A., Kim, M., Montalvo, W., Al-Shamkhani, A., Allison, J.P., Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production. PloS one, 6, 2011, e19499.
12. Dahal, L.N., Dou, L., Hussain, K., Liu, R., Earley, A., Cox, K.L., Murinello, S., Tracy, I., Forconi, F., Steele, A.J., et al. STING activation reverses lymphoma-mediated resistance to antibody immunotherapy. Cancer Res. 77 (2017), 3619–3631.
13. Dahan, R., Sega, E., Engelhardt, J., Selby, M., Korman, A.J., Ravetch, J.V., FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell 28 (2015), 285–295.
14. De Simone, M., Arrigoni, A., Rossetti, G., Gruarin, P., Ranzani, V., Politano, C., Bonnal, R.J.P., Provasi, E., Sarnicola, M.L., Panzeri, I., et al. Transcriptional landscape of human tissue lymphocytes unveils uniqueness of tumor-infiltrating T regulatory cells. Immunity 45 (2016), 1135–1147.
15. Elpek, K.G., Yolcu, E.S., Franke, D.D., Lacelle, C., Schabowsky, R.H., Shirwan, H., Ex vivo expansion of CD4+CD25+FoxP3+ T regulatory cells based on synergy between IL-2 and 4-1BB signaling. J. Immunol. 179 (2007), 7295–7304.
16. French, R.R., Chan, H.T., Tutt, A.L., Glennie, M.J., CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nat. Med. 5 (1999), 548–553.
17. Furness, A.J., Vargas, F.A., Peggs, K.S., Quezada, S.A., Impact of tumour microenvironment and Fc receptors on the activity of immunomodulatory antibodies. Trends Immunol. 35 (2014), 290–298.
18. Gavin, M.A., Clarke, S.R., Negrou, E., Gallegos, A., Rudensky, A., Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat. Immunol. 3 (2002), 33–41.
19. Haynes, N.M., Hawkins, E.D., Li, M., McLaughlin, N.M., Hämmerling, G.J., Schwendener, R., Winoto, A., Wensky, A., Yagita, H., Takeda, K., et al. CD11c+ dendritic cells and B cells contribute to the tumoricidal activity of anti-DR5 antibody therapy in established tumors. J. Immunol. 185 (2010), 532–541.
20. Hodi, F.S., O'Day, S.J., McDermott, D.F., Weber, R.W., Sosman, J.A., Haanen, J.B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J.C., et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363 (2010), 711–723.
21. Li, F., Ravetch, J.V., Inhibitory Fcγ receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333 (2011), 1030–1034.
22. Li, F., Ravetch, J.V., Apoptotic and antitumor activity of death receptor antibodies require inhibitory Fcγ receptor engagement. Proc. Natl. Acad. Sci. USA 109 (2012), 10966–10971.
23. Li, F., Ravetch, J.V., A general requirement for FcγRIIB co-engagement of agonistic anti-TNFR antibodies. Cell Cycle 11 (2012), 3343–3344.
24. Lim, S.H., Vaughan, A.T., Ashton-Key, M., Williams, E.L., Dixon, S.V., Chan, H.T., Beers, S.A., French, R.R., Cox, K.L., Davies, A.J., et al. Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy. Blood 118 (2011), 2530–2540.
25. Lode, H.N., Xiang, R., Varki, N.M., Dolman, C.S., Gillies, S.D., Reisfeld, R.A., Targeted interleukin-2 therapy for spontaneous neuroblastoma metastases to bone marrow. J. Natl. Cancer Inst. 89 (1997), 1586–1594.
26. Marabelle, A., Kohrt, H., Sagiv-Barfi, I., Ajami, B., Axtell, R.C., Zhou, G., Rajapaksa, R., Green, M.R., Torchia, J., Brody, J., et al. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J. Clin. Invest. 123 (2013), 2447–2463.
27. Marson, A., Kretschmer, K., Frampton, G.M., Jacobsen, E.S., Polansky, J.K., MacIsaac, K.D., Levine, S.S., Fraenkel, E., von Boehmer, H., Young, R.A., Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445 (2007), 931–935.
28. McHugh, R.S., Whitters, M.J., Piccirillo, C.A., Young, D.A., Shevach, E.M., Collins, M., Byrne, M.C., CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 16 (2002), 311–323.
29. Melero, I., Hirschhorn-Cymerman, D., Morales-Kastresana, A., Sanmamed, M.F., Wolchok, J.D., Agonist antibodies to TNFR molecules that costimulate T and NK cells. Clin. Cancer Res. 19 (2013), 1044–1053.
30. Middendorp, S., Xiao, Y., Song, J.Y., Peperzak, V., Krijger, P.H., Jacobs, H., Borst, J., Mice deficient for CD137 ligand are predisposed to develop germinal center-derived B-cell lymphoma. Blood 114 (2009), 2280–2289.
31. Mimoto, F., Katada, H., Kadono, S., Igawa, T., Kuramochi, T., Muraoka, M., Wada, Y., Haraya, K., Miyazaki, T., Hattori, K., Engineered antibody Fc variant with selectively enhanced FcgammaRIIb binding over both FcgammaRIIa(R131) and FcgammaRIIa(H131). Protein Eng. Des. Sel., 26, 2013, 589–598.
32. Minard-Colin, V., Xiu, Y., Poe, J.C., Horikawa, M., Magro, C.M., Hamaguchi, Y., Haas, K.M., Tedder, T.F., Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcgammaRI, FcgammaRIII, and FcgammaRIV. Blood 112 (2008), 1205–1213.
33. Molckovsky, A., Siu, L.L., First-in-class, first-in-human phase I results of targeted agents: highlights of the 2008 American society of clinical oncology meeting. J. Hematol. Oncol., 1, 2008, 20.
34. Moore, M.W., Carbone, F.R., Bevan, M.J., Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell 54 (1988), 777–785.
35. Nimmerjahn, F., Ravetch, J.V., Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310 (2005), 1510–1512.
36. Plitas, G., Konopacki, C., Wu, K., Bos, P.D., Morrow, M., Putintseva, E.V., Chudakov, D.M., Rudensky, A.Y., Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer. Immunity 45 (2016), 1122–1134.
37. Romano, E., Kusio-Kobialka, M., Foukas, P.G., Baumgaertner, P., Meyer, C., Ballabeni, P., Michielin, O., Weide, B., Romero, P., Speiser, D.E., Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. Proc. Natl. Acad. Sci. USA 112 (2015), 6140–6145.
38. Rubtsov, Y.P., Rasmussen, J.P., Chi, E.Y., Fontenot, J., Castelli, L., Ye, X., Treuting, P., Siewe, L., Roers, A., Henderson, W.R. Jr., et al. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28 (2008), 546–558.
39. Segal, N.H., Gopal, A.K., Bhatia, S., Kohrt, H., Levy, R., Pishvaian, M.J., Houot, R., Bartlett, N., Nghiem, N., Kronenberg, S.A., et al. A phase 1 study of PF-05082566 (anti-4-1BB) in patients with advanced cancer. J. Clin. Oncol., 32, 2014, 3007.
40. Simpson, T.R., Li, F., Montalvo-Ortiz, W., Sepulveda, M.A., Bergerhoff, K., Arce, F., Roddie, C., Henry, J.Y., Yagita, H., Wolchok, J.D., et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J. Exp. Med. 210 (2013), 1695–1710.
41. Snell, L.M., Lin, G.H., McPherson, A.J., Moraes, T.J., Watts, T.H., T-cell intrinsic effects of GITR and 4-1BB during viral infection and cancer immunotherapy. Immunol. Rev. 244 (2011), 197–217.
42. Taraban, V.Y., Rowley, T.F., O'Brien, L., Chan, H.T., Haswell, L.E., Green, M.H., Tutt, A.L., Glennie, M.J., Al-Shamkhani, A., Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses. Eur. J. Immunol. 32 (2002), 3617–3627.
43. Taraban, V.Y., Ferdinand, J.R., Al-Shamkhani, A., Expression of TNFRSF25 on conventional T cells and Tregs. J. Clin. Invest. 121 (2011), 463–464 author reply 465.
44. Tipton, T.R., Mockridge, C.I., French, R.R., Tutt, A.L., Cragg, M.S., Beers, S.A., Anti-mouse FcγRIV antibody 9E9 also blocks FcγRIII in vivo. Blood 126 (2015), 2643–2645.
45. Topalian, S.L., Hodi, F.S., Brahmer, J.R., Gettinger, S.N., Smith, D.C., McDermott, D.F., Powderly, J.D., Carvajal, R.D., Sosman, J.A., Atkins, M.B., et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366 (2012), 2443–2454.
46. Vonderheide, R.H., Glennie, M.J., Agonistic CD40 antibodies and cancer therapy. Clin. Cancer Res. 19 (2013), 1035–1043.
47. 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 FcγRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody. J. Immunol. 187 (2011), 1754–1763.
48. White, A.L., Beers, S.A., Cragg, M.S., FcγRIIB as a key determinant of agonistic antibody efficacy. Curr. Top. Microbiol. Immunol. 382 (2014), 355–372.
49. 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. Fcγ receptor dependency of agonistic CD40 antibody in lymphoma therapy can be overcome through antibody multimerization. J. Immunol. 193 (2014), 1828–1835.
50. 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.
51. Williams, E.L., Dunn, S.N., James, S., Johnson, P.W., Cragg, M.S., Glennie, M.J., Gray, J.C., Immunomodulatory monoclonal antibodies combined with peptide vaccination provide potent immunotherapy in an aggressive murine neuroblastoma model. Clin. Cancer Res. 19 (2013), 3545–3555.
52. 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.
53. Zheng, G., Wang, B., Chen, A., The 4-1BB costimulation augments the proliferation of CD4+CD25+ regulatory T cells. J. Immunol. 173 (2004), 2428–2434.