Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity

go back to reference Wang C, Lin GH, McPherson AJ, Watts TH (2009) Immune regulation by 4-1BB and 4-1BBL: complexities and challenges. Immunol Rev 229(1):192–215. doi:10.1111/j.1600-065X.2009.00765.x PubMedCrossRef Wang C, Lin GH, McPherson AJ, Watts TH (2009) Immune regulation by 4-1BB and 4-1BBL: complexities and challenges. Immunol Rev 229(1):192–215. doi:10.​1111/​j.​1600-065X.​2009.​00765.​x PubMedCrossRef

go back to reference Broll K, Richter G, Pauly S, Hofstaedter F, Schwarz H (2001) CD137 expression in tumor vessel walls. High correlation with malignant tumors. Am J Clin Pathol 115(4):543–549. doi:10.1309/6U88-357U-UKJ5-YPT3 PubMedCrossRef Broll K, Richter G, Pauly S, Hofstaedter F, Schwarz H (2001) CD137 expression in tumor vessel walls. High correlation with malignant tumors. Am J Clin Pathol 115(4):543–549. doi:10.​1309/​6U88-357U-UKJ5-YPT3 PubMedCrossRef

go back to reference Seaman S, Stevens J, Yang MY, Logsdon D, Graff-Cherry C, St Croix B (2007) Genes that distinguish physiological and pathological angiogenesis. Cancer Cell 11(6):539–554. doi:10.1016/j.ccr.2007.04.017 PubMedCrossRef Seaman S, Stevens J, Yang MY, Logsdon D, Graff-Cherry C, St Croix B (2007) Genes that distinguish physiological and pathological angiogenesis. Cancer Cell 11(6):539–554. doi:10.​1016/​j.​ccr.​2007.​04.​017 PubMedCrossRef

go back to reference Olofsson PS, Soderstrom LA, Wagsater D, Sheikine Y, Ocaya P, Lang F, Rabu C, Chen L, Rudling M, Aukrust P, Hedin U, Paulsson-Berne G, Sirsjo A, Hansson GK (2008) CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice. Circulation 117(10):1292–1301. doi:10.1161/CIRCULATIONAHA.107.699173 PubMedCrossRef Olofsson PS, Soderstrom LA, Wagsater D, Sheikine Y, Ocaya P, Lang F, Rabu C, Chen L, Rudling M, Aukrust P, Hedin U, Paulsson-Berne G, Sirsjo A, Hansson GK (2008) CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice. Circulation 117(10):1292–1301. doi:10.​1161/​CIRCULATIONAHA.​107.​699173 PubMedCrossRef

go back to reference Dawicki W, Bertram EM, Sharpe AH, Watts TH (2004) 4–1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses. J Immunol 173(10):5944–5951PubMed Dawicki W, Bertram EM, Sharpe AH, Watts TH (2004) 4–1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses. J Immunol 173(10):5944–5951PubMed

go back to reference Pollok KE, Kim YJ, Zhou Z, Hurtado J, Kim KK, Pickard RT, Kwon BS (1993) Inducible T cell antigen 4–1BB. Analysis of expression and function. J Immunol 150(3):771–781PubMed Pollok KE, Kim YJ, Zhou Z, Hurtado J, Kim KK, Pickard RT, Kwon BS (1993) Inducible T cell antigen 4–1BB. Analysis of expression and function. J Immunol 150(3):771–781PubMed

go back to reference Chan FK (2007) Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling. Cytokine 37(2):101–107. doi:10.1016/j.cyto.2007.03.005 PubMedCrossRef Chan FK (2007) Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling. Cytokine 37(2):101–107. doi:10.​1016/​j.​cyto.​2007.​03.​005 PubMedCrossRef

go back to reference Michel J, Langstein J, Hofstadter F, Schwarz H (1998) A soluble form of CD137 (ILA/4-1BB), a member of the TNF receptor family, is released by activated lymphocytes and is detectable in sera of patients with rheumatoid arthritis. Eur J Immunol 28(1):290–295. doi:10.1002/(SICI)1521-4141(199801)28:01<290:AID-IMMU290>3.0.CO;2-S PubMedCrossRef Michel J, Langstein J, Hofstadter F, Schwarz H (1998) A soluble form of CD137 (ILA/4-1BB), a member of the TNF receptor family, is released by activated lymphocytes and is detectable in sera of patients with rheumatoid arthritis. Eur J Immunol 28(1):290–295. doi:10.​1002/​(SICI)1521-4141(199801)28:​01<290:​AID-IMMU290>3.​0.​CO;2-S PubMedCrossRef

go back to reference Furtner M, Straub RH, Kruger S, Schwarz H (2005) Levels of soluble CD137 are enhanced in sera of leukemia and lymphoma patients and are strongly associated with chronic lymphocytic leukemia. Leukemia 19(5):883–885. doi:10.1038/sj.leu.2403675 PubMedCrossRef Furtner M, Straub RH, Kruger S, Schwarz H (2005) Levels of soluble CD137 are enhanced in sera of leukemia and lymphoma patients and are strongly associated with chronic lymphocytic leukemia. Leukemia 19(5):883–885. doi:10.​1038/​sj.​leu.​2403675 PubMedCrossRef

go back to reference Hentschel N, Krusch M, Kiener PA, Kolb HJ, Salih HR, Schmetzer HM (2006) Serum levels of sCD137 (4–1BB) ligand are prognostic factors for progression in acute myeloid leukemia but not in non-Hodgkin’s lymphoma. Eur J Haematol 77(2):91–101. doi:10.1111/j.1600-0609.2006.00679.x PubMedCrossRef Hentschel N, Krusch M, Kiener PA, Kolb HJ, Salih HR, Schmetzer HM (2006) Serum levels of sCD137 (4–1BB) ligand are prognostic factors for progression in acute myeloid leukemia but not in non-Hodgkin’s lymphoma. Eur J Haematol 77(2):91–101. doi:10.​1111/​j.​1600-0609.​2006.​00679.​x PubMedCrossRef

go back to reference Sabbagh L, Pulle G, Liu Y, Tsitsikov EN, Watts TH (2008) ERK-dependent Bim modulation downstream of the 4-1BB-TRAF1 signaling axis is a critical mediator of CD8 T cell survival in vivo. J Immunol 180(12):8093–8101PubMed Sabbagh L, Pulle G, Liu Y, Tsitsikov EN, Watts TH (2008) ERK-dependent Bim modulation downstream of the 4-1BB-TRAF1 signaling axis is a critical mediator of CD8 T cell survival in vivo. J Immunol 180(12):8093–8101PubMed

go back to reference Croft M (2009) The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol 9(4):271–285. doi:10.1038/nri2526 PubMedCrossRef Croft M (2009) The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol 9(4):271–285. doi:10.​1038/​nri2526 PubMedCrossRef

go back to reference Wang S, Chen L (2011) Immunobiology of cancer therapies targeting CD137 and B7-H1/PD-1 cosignal pathways. Curr Top Microbiol Immunol 344:245–267. doi:10.1007/82_2010_81 PubMedCrossRef Wang S, Chen L (2011) Immunobiology of cancer therapies targeting CD137 and B7-H1/PD-1 cosignal pathways. Curr Top Microbiol Immunol 344:245–267. doi:10.​1007/​82_​2010_​81 PubMedCrossRef

go back to reference Lynch DH (2008) The promise of 4-1BB (CD137)-mediated immunomodulation and the immunotherapy of cancer. Immunol Rev 222:277–286. doi:10.1111/j.1600-065X.2008.00621.x PubMedCrossRef Lynch DH (2008) The promise of 4-1BB (CD137)-mediated immunomodulation and the immunotherapy of cancer. Immunol Rev 222:277–286. doi:10.​1111/​j.​1600-065X.​2008.​00621.​x PubMedCrossRef

go back to reference Palazon A, Teijeira A, Martinez-Forero I, Hervas-Stubbs S, Roncal C, Penuelas I, Dubrot J, Morales-Kastresana A, Perez-Gracia JL, Ochoa MC, Ochoa-Callejero L, Martinez A, Luque A, Dinchuk J, Rouzaut A, Jure-Kunkel M, Melero I (2011) Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes. Cancer Res 71(3):801–811. doi:10.1158/0008-5472.CAN-10-1733 PubMedCrossRef Palazon A, Teijeira A, Martinez-Forero I, Hervas-Stubbs S, Roncal C, Penuelas I, Dubrot J, Morales-Kastresana A, Perez-Gracia JL, Ochoa MC, Ochoa-Callejero L, Martinez A, Luque A, Dinchuk J, Rouzaut A, Jure-Kunkel M, Melero I (2011) Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes. Cancer Res 71(3):801–811. doi:10.​1158/​0008-5472.​CAN-10-1733 PubMedCrossRef

go back to reference Vinay DS, Cha K, Kwon BS (2006) Dual immunoregulatory pathways of 4-1BB signaling. J Mol Med (Berl) 84(9):726–736. doi:10.1007/s00109-006-0072-2 CrossRef Vinay DS, Cha K, Kwon BS (2006) Dual immunoregulatory pathways of 4-1BB signaling. J Mol Med (Berl) 84(9):726–736. doi:10.​1007/​s00109-006-0072-2 CrossRef

go back to reference Niu L, Strahotin S, Hewes B, Zhang B, Zhang Y, Archer D, Spencer T, Dillehay D, Kwon B, Chen L, Vella AT, Mittler RS (2007) Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice. J Immunol 178(7):4194–4213PubMed Niu L, Strahotin S, Hewes B, Zhang B, Zhang Y, Archer D, Spencer T, Dillehay D, Kwon B, Chen L, Vella AT, Mittler RS (2007) Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice. J Immunol 178(7):4194–4213PubMed

go back to reference Dubrot J, Palazon A, Alfaro C, Azpilikueta A, Ochoa MC, Rouzaut A, Martinez-Forero I, Teijeira A, Berraondo P, Le Bon A, Hervas-Stubbs S, Melero I (2011) Intratumoral injection of interferon-alpha and systemic delivery of agonist anti-CD137 monoclonal antibodies synergize for immunotherapy. Int J Cancer 128(1):105–118. doi:10.1002/ijc.25333 PubMedCrossRef Dubrot J, Palazon A, Alfaro C, Azpilikueta A, Ochoa MC, Rouzaut A, Martinez-Forero I, Teijeira A, Berraondo P, Le Bon A, Hervas-Stubbs S, Melero I (2011) Intratumoral injection of interferon-alpha and systemic delivery of agonist anti-CD137 monoclonal antibodies synergize for immunotherapy. Int J Cancer 128(1):105–118. doi:10.​1002/​ijc.​25333 PubMedCrossRef

go back to reference Sznol M, Hodi FS, Margolin K, McDermott DF, Ernestoff S, Kirkwood JM (2008) Phase I study of BMS-663513, a fully human anti-CD137 agonist monoclonal antibody, in patients with advanced cancer. J Clin Oncol 26(115S):3007 Sznol M, Hodi FS, Margolin K, McDermott DF, Ernestoff S, Kirkwood JM (2008) Phase I study of BMS-663513, a fully human anti-CD137 agonist monoclonal antibody, in patients with advanced cancer. J Clin Oncol 26(115S):3007

go back to reference Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I (2010) Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol 37(5):508–516. doi:10.1053/j.seminoncol.2010.09.008 PubMedCrossRef Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I (2010) Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol 37(5):508–516. doi:10.​1053/​j.​seminoncol.​2010.​09.​008 PubMedCrossRef

go back to reference Chen SJ, Foster WR, Jure-Kunkel MN, Girit E, Abraham R, Hefta LJ, Gao S, Yonan CR, Lin JH, Dambach DM (2008) Cloning, expression and characterization of monkey (Macaca fascicularis) CD137. Vet Immunol Immunopathol 126(3–4):377–381. doi:10.1016/j.vetimm.2008.07.009 PubMedCrossRef Chen SJ, Foster WR, Jure-Kunkel MN, Girit E, Abraham R, Hefta LJ, Gao S, Yonan CR, Lin JH, Dambach DM (2008) Cloning, expression and characterization of monkey (Macaca fascicularis) CD137. Vet Immunol Immunopathol 126(3–4):377–381. doi:10.​1016/​j.​vetimm.​2008.​07.​009 PubMedCrossRef

go back to reference King M, Pearson T, Shultz LD, Leif J, Bottino R, Trucco M, Atkinson MA, Wasserfall C, Herold KC, Woodland RT, Schmidt MR, Woda BA, Thompson MJ, Rossini AA, Greiner DL (2008) A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene. Clin Immunol 126(3):303–314. doi:10.1016/j.clim.2007.11.001 PubMedCrossRef King M, Pearson T, Shultz LD, Leif J, Bottino R, Trucco M, Atkinson MA, Wasserfall C, Herold KC, Woodland RT, Schmidt MR, Woda BA, Thompson MJ, Rossini AA, Greiner DL (2008) A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene. Clin Immunol 126(3):303–314. doi:10.​1016/​j.​clim.​2007.​11.​001 PubMedCrossRef

go back to reference Pitcher CJ, Hagen SI, Walker JM, Lum R, Mitchell BL, Maino VC, Axthelm MK, Picker LJ (2002) Development and homeostasis of T cell memory in rhesus macaque. J Immunol 168(1):29–43PubMed Pitcher CJ, Hagen SI, Walker JM, Lum R, Mitchell BL, Maino VC, Axthelm MK, Picker LJ (2002) Development and homeostasis of T cell memory in rhesus macaque. J Immunol 168(1):29–43PubMed

go back to reference Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7(2):118–130. doi:10.1038/nri2017 PubMedCrossRef Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7(2):118–130. doi:10.​1038/​nri2017 PubMedCrossRef

go back to reference Iwanuma Y, Chen FA, Egilmez NK, Takita H, Bankert RB (1997) Antitumor immune response of human peripheral blood lymphocytes coengrafted with tumor into severe combined immunodeficient mice. Cancer Res 57(14):2937–2942PubMed Iwanuma Y, Chen FA, Egilmez NK, Takita H, Bankert RB (1997) Antitumor immune response of human peripheral blood lymphocytes coengrafted with tumor into severe combined immunodeficient mice. Cancer Res 57(14):2937–2942PubMed

go back to reference Sondak VK, Smalley KS, Kudchadkar R, Grippon S, Kirkpatrick P (2011) Ipilimumab. Nat Rev Drug Discov 10(6):411–412. doi:10.1038/nrd3463 PubMedCrossRef Sondak VK, Smalley KS, Kudchadkar R, Grippon S, Kirkpatrick P (2011) Ipilimumab. Nat Rev Drug Discov 10(6):411–412. doi:10.​1038/​nrd3463 PubMedCrossRef

go back to reference Lesterhuis WJ, Haanen JB, Punt CJ (2011) Cancer immunotherapy—revisited. Nat Rev Drug Discov 10(8):591–600. doi:10.1038/nrd3500 PubMedCrossRef Lesterhuis WJ, Haanen JB, Punt CJ (2011) Cancer immunotherapy—revisited. Nat Rev Drug Discov 10(8):591–600. doi:10.​1038/​nrd3500 PubMedCrossRef

go back to reference Cheever MA (2008) Twelve immunotherapy drugs that could cure cancers. Immunol Rev 222:357–368. doi:10.1111/j.1600-065X.2008.00604.x PubMedCrossRef Cheever MA (2008) Twelve immunotherapy drugs that could cure cancers. Immunol Rev 222:357–368. doi:10.​1111/​j.​1600-065X.​2008.​00604.​x PubMedCrossRef

go back to reference Schabowsky RH, Elpek KG, Madireddi S, Sharma RK, Yolcu ES, Bandura-Morgan L, Miller R, MacLeod KJ, Mittler RS, Shirwan H (2009) A novel form of 4-1BBL has better immunomodulatory activity than an agonistic anti-4-1BB Ab without Ab-associated severe toxicity. Vaccine 28(2):512–522. doi:10.1016/j.vaccine.2009.09.127 PubMedCrossRef Schabowsky RH, Elpek KG, Madireddi S, Sharma RK, Yolcu ES, Bandura-Morgan L, Miller R, MacLeod KJ, Mittler RS, Shirwan H (2009) A novel form of 4-1BBL has better immunomodulatory activity than an agonistic anti-4-1BB Ab without Ab-associated severe toxicity. Vaccine 28(2):512–522. doi:10.​1016/​j.​vaccine.​2009.​09.​127 PubMedCrossRef

go back to reference McNamara JO, Kolonias D, Pastor F, Mittler RS, Chen L, Giangrande PH, Sullenger B, Gilboa E (2008) Multivalent 4–1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J Clin Invest 118(1):376–386. doi:10.1172/JCI33365 PubMedCrossRef McNamara JO, Kolonias D, Pastor F, Mittler RS, Chen L, Giangrande PH, Sullenger B, Gilboa E (2008) Multivalent 4–1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J Clin Invest 118(1):376–386. doi:10.​1172/​JCI33365 PubMedCrossRef

go back to reference Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, Samanta M, Lakhal M, Gloss B, Danet-Desnoyers G, Campana D, Riley JL, Grupp SA, June CH (2009) Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther 17(8):1453–1464. doi:10.1038/mt.2009.83 PubMedCrossRef Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, Samanta M, Lakhal M, Gloss B, Danet-Desnoyers G, Campana D, Riley JL, Grupp SA, June CH (2009) Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther 17(8):1453–1464. doi:10.​1038/​mt.​2009.​83 PubMedCrossRef

go back to reference Song DG, Ye Q, Carpenito C, Poussin M, Wang LP, Ji C, Figini M, June CH, Coukos G, Powell DJ Jr (2011) In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB). Cancer Res 71(13):4617–4627. doi:10.1158/0008-5472.CAN-11-0422 PubMedCrossRef Song DG, Ye Q, Carpenito C, Poussin M, Wang LP, Ji C, Figini M, June CH, Coukos G, Powell DJ Jr (2011) In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB). Cancer Res 71(13):4617–4627. doi:10.​1158/​0008-5472.​CAN-11-0422 PubMedCrossRef

go back to reference Finney HM, Akbar AN, Lawson AD (2004) Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J Immunol 172(1):104–113PubMed Finney HM, Akbar AN, Lawson AD (2004) Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J Immunol 172(1):104–113PubMed

go back to reference Sadelain M, Brentjens R, Riviere I (2009) The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol 21(2):215–223. doi:10.1016/j.coi.2009.02.009 PubMedCrossRef Sadelain M, Brentjens R, Riviere I (2009) The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol 21(2):215–223. doi:10.​1016/​j.​coi.​2009.​02.​009 PubMedCrossRef

go back to reference Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH (2011) T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 3(95):95ra73. doi:10.1126/scitranslmed.3002842 PubMedCrossRef Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH (2011) T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 3(95):95ra73. doi:10.​1126/​scitranslmed.​3002842 PubMedCrossRef

go back to reference Porter DL, Levine BL, Kalos M, Bagg A, June CH (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365(8):725–733. doi:10.1056/NEJMoa1103849 PubMedCrossRef Porter DL, Levine BL, Kalos M, Bagg A, June CH (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365(8):725–733. doi:10.​1056/​NEJMoa1103849 PubMedCrossRef

go back to reference Tan JT, Whitmire JK, Ahmed R, Pearson TC, Larsen CP (1999) 4–1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. J Immunol 163(9):4859–4868PubMed Tan JT, Whitmire JK, Ahmed R, Pearson TC, Larsen CP (1999) 4–1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. J Immunol 163(9):4859–4868PubMed

go back to reference Zhu Y, Zhu G, Luo L, Flies AS, Chen L (2007) CD137 stimulation delivers an antigen-independent growth signal for T lymphocytes with memory phenotype. Blood 109(11):4882–4889. doi:10.1182/blood-2006-10-043463 PubMedCrossRef Zhu Y, Zhu G, Luo L, Flies AS, Chen L (2007) CD137 stimulation delivers an antigen-independent growth signal for T lymphocytes with memory phenotype. Blood 109(11):4882–4889. doi:10.​1182/​blood-2006-10-043463 PubMedCrossRef

go back to reference Hong HJ, Lee JW, Park SS, Kang YJ, Chang SY, Kim KM, Kim JO, Murthy KK, Payne JS, Yoon SK, Park MJ, Kim IC, Kim JG, Kang CY (2000) A humanized anti-4-1BB monoclonal antibody suppresses antigen-induced humoral immune response in nonhuman primates. J Immunother 23(6):613–621PubMedCrossRef Hong HJ, Lee JW, Park SS, Kang YJ, Chang SY, Kim KM, Kim JO, Murthy KK, Payne JS, Yoon SK, Park MJ, Kim IC, Kim JG, Kang CY (2000) A humanized anti-4-1BB monoclonal antibody suppresses antigen-induced humoral immune response in nonhuman primates. J Immunother 23(6):613–621PubMedCrossRef

go back to reference Calarota SA, Hokey DA, Dai A, Jure-Kunkel MN, Balimane P, Weiner DB (2008) Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB costimulatory molecule. Vaccine 26(25):3121–3134. doi:10.1016/j.vaccine.2008.02.017 PubMedCrossRef Calarota SA, Hokey DA, Dai A, Jure-Kunkel MN, Balimane P, Weiner DB (2008) Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB costimulatory molecule. Vaccine 26(25):3121–3134. doi:10.​1016/​j.​vaccine.​2008.​02.​017 PubMedCrossRef

go back to reference Hirao LA, Hokey DA, Morrow MP, Jure-Kunkel MN, Weiner DB (2011) Immune modulation through 4-1BB enhances SIV vaccine protection in non-human primates against SIVmac251 challenge. PLoS ONE 6(9):e24250. doi:10.1371/journal.pone.0024250 PubMedCrossRef Hirao LA, Hokey DA, Morrow MP, Jure-Kunkel MN, Weiner DB (2011) Immune modulation through 4-1BB enhances SIV vaccine protection in non-human primates against SIVmac251 challenge. PLoS ONE 6(9):e24250. doi:10.​1371/​journal.​pone.​0024250 PubMedCrossRef

go back to reference Li F, Ravetch JV (2011) Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333(6045):1030–1034. doi:10.1126/science.1206954 PubMedCrossRef Li F, Ravetch JV (2011) Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333(6045):1030–1034. doi:10.​1126/​science.​1206954 PubMedCrossRef

go back to reference White AL, Chan HT, Roghanian A, French RR, Mockridge CI, Tutt AL, Dixon SV, Ajona D, Verbeek JS, Al-Shamkhani A, Cragg MS, Beers SA, Glennie MJ (2011) Interaction with FcgammaRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody. J Immunol 187(4):1754–1763. doi:10.4049/jimmunol.1101135 PubMedCrossRef White AL, Chan HT, Roghanian A, French RR, Mockridge CI, Tutt AL, Dixon SV, Ajona D, Verbeek JS, Al-Shamkhani A, Cragg MS, Beers SA, Glennie MJ (2011) Interaction with FcgammaRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody. J Immunol 187(4):1754–1763. doi:10.​4049/​jimmunol.​1101135 PubMedCrossRef

go back to reference Gladue RP, Paradis T, Cole SH, Donovan C, Nelson R, Alpert R, Gardner J, Natoli E, Elliott E, Shepard R, Bedian V (2011) 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(7):1009–1017. doi:10.1007/s00262-011-1014-6 PubMedCrossRef Gladue RP, Paradis T, Cole SH, Donovan C, Nelson R, Alpert R, Gardner J, Natoli E, Elliott E, Shepard R, Bedian V (2011) 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(7):1009–1017. doi:10.​1007/​s00262-011-1014-6 PubMedCrossRef

go back to reference Hunter TB, Alsarraj M, Gladue RP, Bedian V, Antonia SJ (2007) An agonist antibody specific for CD40 induces dendritic cell maturation and promotes autologous anti-tumour T-cell responses in an in vitro mixed autologous tumour cell/lymph node cell model. Scand J Immunol 65(5):479–486. doi:10.1111/j.1365-3083.2007.01927.x PubMedCrossRef Hunter TB, Alsarraj M, Gladue RP, Bedian V, Antonia SJ (2007) An agonist antibody specific for CD40 induces dendritic cell maturation and promotes autologous anti-tumour T-cell responses in an in vitro mixed autologous tumour cell/lymph node cell model. Scand J Immunol 65(5):479–486. doi:10.​1111/​j.​1365-3083.​2007.​01927.​x PubMedCrossRef

go back to reference Carpenter EL, Mick R, Ruter J, Vonderheide RH (2009) Activation of human B cells by the agonist CD40 antibody CP-870,893 and augmentation with simultaneous toll-like receptor 9 stimulation. J Transl Med 7:93. doi:10.1186/1479-5876-7-93 PubMedCrossRef Carpenter EL, Mick R, Ruter J, Vonderheide RH (2009) Activation of human B cells by the agonist CD40 antibody CP-870,893 and augmentation with simultaneous toll-like receptor 9 stimulation. J Transl Med 7:93. doi:10.​1186/​1479-5876-7-93 PubMedCrossRef

go back to reference Ruter J, Antonia SJ, Burris HA, Huhn RD, Vonderheide RH (2010) Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors. Cancer Biol Ther 10(10):983–993. doi:10.4161/cbt.10.10.13251 PubMedCrossRef Ruter J, Antonia SJ, Burris HA, Huhn RD, Vonderheide RH (2010) Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors. Cancer Biol Ther 10(10):983–993. doi:10.​4161/​cbt.​10.​10.​13251 PubMedCrossRef

go back to reference Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O’Dwyer PJ, Vonderheide RH (2011) CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331(6024):1612–1616. doi:10.1126/science.1198443 PubMedCrossRef Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O’Dwyer PJ, Vonderheide RH (2011) CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331(6024):1612–1616. doi:10.​1126/​science.​1198443 PubMedCrossRef

go back to reference Fox BA, Schendel DJ, Butterfield LH, Aamdal S, Allison JP, Ascierto PA, Atkins MB, Bartunkova J, Bergmann L, Berinstein N, Bonorino CC, Borden E, Bramson JL, Britten CM, Cao X, Carson WE, Chang AE, Characiejus D, Choudhury AR, Coukos G, de Gruijl T, Dillman RO, Dolstra H, Dranoff G, Durrant LG, Finke JH, Galon J, Gollob JA, Gouttefangeas C, Grizzi F, Guida M, Hakansson L, Hege K, Herberman RB, Hodi FS, Hoos A, Huber C, Hwu P, Imai K, Jaffee EM, Janetzki S, June CH, Kalinski P, Kaufman HL, Kawakami K, Kawakami Y, Keilholtz U, Khleif SN, Kiessling R, Kotlan B, Kroemer G, Lapointe R, Levitsky HI, Lotze MT, Maccalli C, Maio M, Marschner JP, Mastrangelo MJ, Masucci G, Melero I, Nelief C, Murphy WJ, Nelson B, Nicolini A, Nishimura MI, Odunsi K, Ohashi PS, O’Donnell-Tormey J, Old LJ, Ottensmeier C, Papamichail M, Parmiani G, Pawelec G, Proietti E, Qin S, Rees R, Ribas A, Ridolfi R, Ritter G, Rivoltini L, Romero PJ, Salem ML, Scheper RJ, Seliger B, Sharma P, Shiku H, Singh-Jasuja H, Song W, Straten PT, Tahara H, Tian Z, van Der Burg SH, von Hoegen P, Wang E, Welters MJ, Winter H, Withington T, Wolchok JD, Xiao W, Zitvogel L, Zwierzina H, Marincola FM, Gajewski TF, Wigginton JM, Disis ML (2011) Defining the critical hurdles in cancer immunotherapy. J Transl Med 9(1):214. doi:10.1186/1479-5876-9-214 PubMedCrossRef Fox BA, Schendel DJ, Butterfield LH, Aamdal S, Allison JP, Ascierto PA, Atkins MB, Bartunkova J, Bergmann L, Berinstein N, Bonorino CC, Borden E, Bramson JL, Britten CM, Cao X, Carson WE, Chang AE, Characiejus D, Choudhury AR, Coukos G, de Gruijl T, Dillman RO, Dolstra H, Dranoff G, Durrant LG, Finke JH, Galon J, Gollob JA, Gouttefangeas C, Grizzi F, Guida M, Hakansson L, Hege K, Herberman RB, Hodi FS, Hoos A, Huber C, Hwu P, Imai K, Jaffee EM, Janetzki S, June CH, Kalinski P, Kaufman HL, Kawakami K, Kawakami Y, Keilholtz U, Khleif SN, Kiessling R, Kotlan B, Kroemer G, Lapointe R, Levitsky HI, Lotze MT, Maccalli C, Maio M, Marschner JP, Mastrangelo MJ, Masucci G, Melero I, Nelief C, Murphy WJ, Nelson B, Nicolini A, Nishimura MI, Odunsi K, Ohashi PS, O’Donnell-Tormey J, Old LJ, Ottensmeier C, Papamichail M, Parmiani G, Pawelec G, Proietti E, Qin S, Rees R, Ribas A, Ridolfi R, Ritter G, Rivoltini L, Romero PJ, Salem ML, Scheper RJ, Seliger B, Sharma P, Shiku H, Singh-Jasuja H, Song W, Straten PT, Tahara H, Tian Z, van Der Burg SH, von Hoegen P, Wang E, Welters MJ, Winter H, Withington T, Wolchok JD, Xiao W, Zitvogel L, Zwierzina H, Marincola FM, Gajewski TF, Wigginton JM, Disis ML (2011) Defining the critical hurdles in cancer immunotherapy. J Transl Med 9(1):214. doi:10.​1186/​1479-5876-9-214 PubMedCrossRef