Anti-CD137 enhances anti-CD20 therapy of systemic B-cell lymphoma with altered immune homeostasis but negligible toxicity

References

• Maloney DG. Anti-CD20 antibody therapy for B-cell lymphomas. N Eng J Med 2012; 366:2008-16; PMID:22621628; http://dx.doi.org/10.1056/NEJMct1114348
   PubMed Web of Science ®Google Scholar
• Blombery PA, Wall M, Seymour JF. The molecular pathogenesis of B-cell non-Hodgkin lymphoma. Eur J Haematol 2015; 95:280-93; PMID:25996166; http://dx.doi.org/10.1111/ejh.12589
   PubMed Web of Science ®Google Scholar
• Azim HA, Jr, de Azambuja E, Colozza M, Bines J, Piccart MJ. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Annals Oncol 2011; 22:1939-47; PMID:21289366; http://dx.doi.org/10.1093/annonc/mdq683
   PubMed Web of Science ®Google Scholar
• Stone JB, DeAngelis LM. Cancer-treatment-induced neurotoxicity-focus on newer treatments. Nat Rev Clin Oncol. 2016 Feb; 13(2):92–105; PMID:26391778; http://dx.doi.org/10.1038/nrclinonc.2015.152
   PubMedGoogle Scholar
• Minard-Colin V, Xiu Y, Poe JC, Horikawa M, Magro CM, Hamaguchi Y, Haas KM, Tedder TF. Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcgammaRI, FcgammaRIII, and FcgammaRIV. Blood 2008; 112:1205-13; PMID:18495955; http://dx.doi.org/10.1182/blood-2008-01-135160
   PubMed Web of Science ®Google Scholar
• Lim SH, Levy R. Translational medicine in action: anti-CD20 therapy in lymphoma. J Immunol 2014; 193:1519-24; PMID:25086174; http://dx.doi.org/10.4049/jimmunol.1490027
   PubMed Web of Science ®Google Scholar
• Kohrt HE, Thielens A, Marabelle A, Sagiv-Barfi I, Sola C, Chanuc F, Fuseri N, Bonnafous C, Czerwinski D, Rajapaksa A et al. Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies. Blood 2014; 123:678-86; PMID:24326534; http://dx.doi.org/10.1182/blood-2013-08-519199
   PubMed Web of Science ®Google Scholar
• Sanmamed MF, Pastor F, Rodriguez A, Perez-Gracia JL, Rodriguez-Ruiz ME, Jure-Kunkel M, Melero I. Agonists of co-stimulation in cancer immunotherapy directed against CD137, OX40, GITR, CD27, CD28, and ICOS. Seminars Oncol 2015; 42:640-55; PMID:26320067; http://dx.doi.org/10.1053/j.seminoncol.2015.05.014
   PubMed Web of Science ®Google Scholar
• Yonezawa A, Dutt S, Chester C, Kim J, Kohrt HE. Boosting cancer immunotherapy with anti-CD137 antibody therapy. Clin Cancer Res 2015; 21:3113-20; PMID:25908780; http://dx.doi.org/10.1158/1078-0432.CCR-15-0263
   PubMed Web of Science ®Google Scholar
• Kohrt HE, Houot R, Goldstein MJ, Weiskopf K, Alizadeh AA, Brody J, Müller A, Pachynski R, Czerwinski D, Coutre S et al. CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies. Blood 2011; 117:2423-32; PMID:21193697; http://dx.doi.org/10.1182/blood-2010-08-301945
   PubMed Web of Science ®Google Scholar
• Kohrt HE, Houot R, Weiskopf K, Goldstein MJ, Scheeren F, Czerwinski D, Colevas AD, Weng WK, Clarke MF, Carlson RW et al. Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer. J Clin Invest 2012; 122:1066-75; PMID:22326955; http://dx.doi.org/10.1172/JCI61226
   PubMed Web of Science ®Google Scholar
• Kohrt HE, Colevas AD, Houot R, Weiskopf K, Goldstein MJ, Lund P, Mueller A, Sagiv-Barfi I, Marabelle A, Lira R et al. Targeting CD137 enhances the efficacy of cetuximab. J Clin Invest 2014; 124:2668-82; PMID:24837434; http://dx.doi.org/10.1172/JCI73014
   PubMed Web of Science ®Google Scholar
• Niu L, Strahotin S, Hewes B, Zhang B, Zhang Y, Archer D, Spencer T, Dillehay D, Kwon B, Chen L et al. Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice. J Immunol 2007; 178:4194-213; PMID:17371976; http://dx.doi.org/10.4049/jimmunol.178.7.4194
   PubMed Web of Science ®Google Scholar
• Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Seminars Oncol 2010; 37:508-16; PMID:21074066; http://dx.doi.org/10.1053/j.seminoncol.2010.09.008
   PubMed Web of Science ®Google Scholar
• Makkouk A, Chester C, Kohrt HE. Rationale for anti-CD137 cancer immunotherapy. Eur J Cancer 2016; 54:112-9; PMID:26751393; http://dx.doi.org/10.1016/j.ejca.2015.09.026
   PubMed Web of Science ®Google Scholar
• Sarikonda G, Sachithanantham S, Manenkova Y, Kupfer T, Posgai A, Wasserfall C, Bernstein P, Straub L, Pagni PP, Schneider D et al. Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice. PloS One 2013; 8:e54712; PMID:23405091; http://dx.doi.org/10.1371/journal.pone.0054712
   PubMedGoogle Scholar
• Wu ZQ, Khan AQ, Shen Y, Wolcott KM, Dawicki W, Watts TH, Mittler RS, Snapper CM. Four-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide-specific immunoglobulin isotype responses to Streptococcus pneumoniae. Infect Immun 2003; 71:196-204; PMID:12496166; http://dx.doi.org/10.1128/IAI.71.1.196-204.2003
   PubMed Web of Science ®Google Scholar
• Bruhns P. Properties of mouse and human IgG receptors and their contribution to disease models. Blood 2012; 119:5640-9; PMID:22535666; http://dx.doi.org/10.1182/blood-2012-01-380121
   PubMed Web of Science ®Google Scholar
• Hazenbos WL, Gessner JE, Hofhuis FM, Kuipers H, Meyer D, Heijnen IA, Schmidt RE, Sandor M, Capel PJ, Daëron M et al. Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice. Immunity 1996; 5:181-8; PMID:8769481; http://dx.doi.org/10.1016/S1074-7613(00)80494-X
   PubMed Web of Science ®Google Scholar
• Nimmerjahn F, Lux A, Albert H, Woigk M, Lehmann C, Dudziak D, Smith P, Ravetch JV. FcgammaRIV deletion reveals its central role for IgG2a and IgG2b activity in vivo. Proc Natl Acad Sci U S A 2010; 107:19396-401; PMID:20974962; http://dx.doi.org/10.1073/pnas.1014515107
   PubMed Web of Science ®Google Scholar
• Terrier B, Ittah M, Tourneur L, Louache F, Soumelis V, Lavie F, Casadevall N, Candon S, Hummel A, Mariette X et al. Late-onset neutropenia following rituximab results from a hematopoietic lineage competition due to an excessive BAFF-induced B-cell recovery. Haematologica 2007; 92:e20-3; PMID:17405749; http://dx.doi.org/10.3324/haematol.11031
   PubMedGoogle Scholar
• Pranzatelli MR, Tate ED, Travelstead AL, Verhulst SJ. Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS. Cytokine 2011; 53:384-9; PMID:21211990; http://dx.doi.org/10.1016/j.cyto.2010.12.004
   PubMed Web of Science ®Google Scholar
• Mueller A, Strange PG. The chemokine receptor, CCR5. Int J Biochem Cell Biol 2004; 36:35-8; PMID:14592532; http://dx.doi.org/10.1016/S1357-2725(03)00172-9
   PubMed Web of Science ®Google Scholar
• Dubrot J, Milheiro F, Alfaro C, Palazon A, Martinez-Forero I, Perez-Gracia JL, Morales-Kastresana A, Romero-Trevejo JL, Ochoa MC, Hervás-Stubbs S et al. Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ. Cancer Immunol Immunotherapy 2010; 59:1223-33; PMID:20336294; http://dx.doi.org/10.1007/s00262-010-0846-9
   PubMed Web of Science ®Google Scholar
• Balogh K, Dudley RH, Cohen RB. Oxidative enzyme activity in skeletal cartilage and bone. Lab Invest 1961; 10:839-45
   Web of Science ®Google Scholar
• Sherwood ME, Flotte TJ. Improved staining method for determining the extent of thermal damage to cells. Lasers Surg Med 2007; 39:128-31; PMID:17163480; http://dx.doi.org/10.1002/lsm.20450
   PubMed Web of Science ®Google Scholar
• Sookoian S, Pirola CJ. Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles in pathogenesis of metabolic syndrome. World J Gastroenterol 2012; 18:3775-81; PMID:22876026; http://dx.doi.org/10.3748/wjg.v18.i29.3775
   PubMed Web of Science ®Google Scholar
• Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 2011; 331:1565-70; PMID:21436444; http://dx.doi.org/10.1126/science.1203486
   PubMed Web of Science ®Google Scholar
• Krasnova Y, Putz EM, Smyth MJ, Souza-Fonseca-Guimaraes F. Bench to bedside: NK cells and control of metastasis. Clin Immunol 2015; PMID:26476139; pii: S1521-6616(15)30050-4; http://dx.doi.org/10.1016/j.clim.2015.10.001
   PubMed Web of Science ®Google Scholar
• Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 2015; 14:561-84; PMID:26228759; http://dx.doi.org/10.1038/nrd4591
   PubMed Web of Science ®Google Scholar
• Smyth MJ, Ngiow SF, Ribas A, Teng MW. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat Rev Clin Oncol 2016; 13:143-58; PMID:26598942; http://dx.doi.org/10.1038/nrclinonc.2015.209
   PubMed Web of Science ®Google Scholar
• Wasmuth JC, Fischer HP, Sauerbruch T, Dumoulin FL. Fatal acute liver failure due to reactivation of hepatitis B following treatment with fludarabine/cyclophosphamide/rituximab for low grade non-Hodgkin's lymphoma. Eur J Med Res 2008; 13:483-6; PMID:19008178
   PubMed Web of Science ®Google Scholar
• Cho YS, Kwon B, Lee TH, Kim TB, Moon KA, La S, Lee J, Lee SD, Oh YM, Moon HB. 4-1 BB stimulation inhibits allergen-specific immunoglobulin E production and airway hyper-reactivity but partially suppresses bronchial eosinophilic inflammation in a mouse asthma model. Clin Exp Allergy 2006; 36:377-85; PMID:16499650; http://dx.doi.org/10.1111/j.1365-2222.2006.02445.x
   PubMed Web of Science ®Google Scholar
• Vinay DS, Lee SJ, Kim CH, Oh HS, Kwon BS. Exposure of a distinct PDCA-1+ (CD317) B cell population to agonistic anti-4-1BB (CD137) inhibits T and B cell responses both in vitro and in vivo. PloS One 2012; 7:e50272; PMID:23185591; http://dx.doi.org/10.1371/journal.pone.0050272
   PubMedGoogle Scholar
• Montalvao F, Garcia Z, Celli S, Breart B, Deguine J, Van Rooijen N, Bousso P. The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging. J Clin Invest 2013; 123:5098-103; PMID:24177426; http://dx.doi.org/10.1172/JCI70972
   PubMed Web of Science ®Google Scholar
• Kienzle G, von Kempis J. CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes. Int Immunol 2000; 12:73-82; PMID:10607752; http://dx.doi.org/10.1093/intimm/12.1.73
   PubMed Web of Science ®Google Scholar
• Perez-Martinez L, Perez-Matute P, Aguilera-Lizarraga J, Rubio-Mediavilla S, Narro J, Recio E, Ochoa-Callejero L, Oteo JA, Blanco JR. Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). J Antimicrobial Chemotherapy 2014; 69:1903-10; PMID:24651825; http://dx.doi.org/10.1093/jac/dku071
   PubMed Web of Science ®Google Scholar
• Palazon A, Teijeira A, Martinez-Forero I, Hervas-Stubbs S, Roncal C, Penuelas I, Dubrot J, Morales-Kastresana A, Pérez-Gracia JL, Ochoa MC et al. Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes. Cancer Res 2011; 71:801-11; PMID:21266358; http://dx.doi.org/10.1158/0008-5472.CAN-10-1733
   PubMed Web of Science ®Google Scholar
• Takai T, Li M, Sylvestre D, Clynes R, Ravetch JV. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell 1994; 76:519-29; PMID:8313472; http://dx.doi.org/10.1016/0092-8674(94)90115-5
   PubMed Web of Science ®Google Scholar
• Bruedigam C, Bagger FO, Heidel FH, Paine Kuhn C, Guignes S, Song A, Austin R, Vu T, Lee E, Riyat S et al. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy. Cell Stem Cell 2014; 15:775-90; PMID:25479751; http://dx.doi.org/10.1016/j.stem.2014.11.010
   PubMed Web of Science ®Google Scholar
• Souza-Fonseca-Guimaraes F, Young A, Mittal D, Martinet L, Bruedigam C, Takeda K, Andoniou CE, Degli-Esposti MA, Hill GR, Smyth MJ. NK cells require IL-28R for optimal in vivo activity. Proc Natl Acad Sci U S A 2015; 112:E2376-84; PMID:25901316; http://dx.doi.org/10.1073/pnas.1424241112
   PubMed Web of Science ®Google Scholar
• Sznol M, Hodi FS, Margolin K, McDermott DF, Ernstoff MS, Kirkwood JM, Wojtaszek C, Feltquate D, Logan T. Phase I study of BMS-663513, a fully human anti-CD137 agonist monoclonal antibody, in patients (pts) with advanced cancer (CA). J Clin Oncol 2008; 26:3007; Abstract number:TPS3107
   Google Scholar
• Melero I, Gangadhar TC, Kohrt HE, Segal NH, Logan T, Urba WJ, Hodi FS, Ott PA, Perez-Garcia JL, Wolchok JD et al. A phase I study of the safety, tolerability, pharmacokinetics, and immunoregulatory activity of urelumab (BMS-663513) in subjects with advanced and/or metastatic solid tumors and relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL). J Clin Oncol 2013; 32
   Google Scholar
• Segal NH, L T, Hodi FS, McDermott D, Melero I, Hamid O, Schmidt H, Robert C, Chiarion-Sileni V, Ascierto PA et al. Results from an integrated safety analysis of urelumab, an agonist anti-CD137 monoclonal antibody. Submitted 2016
   Google Scholar
• Kohrt HE, Godwin JE, Lossos IS, Williams ME, Timmerman J, Link BK, Goldberg SM, McGirr A, Kurland JF, Wigginton JM et al. A phase Ib, open-label, multicenter study of urelumab (BMS-663513) in combination with rituximab in subjects with relapsed/refractory B-cell malignancies. J Clin Oncol 2013; 31; Abstract number:TPS3108
   Web of Science ®Google Scholar
• Segal NH, Gopal AK, Bhatia S, Kohrt HE, Levy R, Pishvaian MJ, Houot R, Bartlett N, Nghiem P, Kronenberg SA. A phase 1 study of PF-05082566 (anti-4-1BB) in patients with advanced cancer. J Clin Oncol 2014; Suppl; abstr 3007; PMID:24934783
   PubMed Web of Science ®Google Scholar
• Gopal AK, Bartlett NL, Levy R, Houot R, Smith SD, Segal NH, Thall AD, Mugundu G, Huang B, Davis C et al. A phase I study of PF-05082566 (anti-4-1BB) + rituximab in patients with CD20+ NHL. J Clin Oncol 2015; Suppl; abstr 3004
   Google Scholar