241
Views
13
CrossRef citations to date
0
Altmetric
Review

Using monoclonal antibodies to stimulate antitumor cellular immunity

, &
Pages 1093-1106 | Published online: 09 Jan 2014

References

  • Reff ME, Carner K, Chambers KS et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood83(2), 435–445 (1994).
  • Glennie MJ, French RR, Cragg MS, Taylor RP. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol. Immunol.44(16), 3823–3837 (2007).
  • Pescovitz MD. Rituximab, an anti-CD20 monoclonal antibody: history and mechanism of action. Am. J. Transplant.6(5 Pt 1), 859–866 (2006).
  • Barok M, Isola J, Palyi-Krekk Z et al. Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance. Mol. Cancer Ther.6(7), 2065–2072 (2007).
  • Carter P, Presta L, Gorman CM et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl Acad. Sci. USA89(10), 4285–4289 (1992).
  • Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N. Engl. J. Med.357(1), 39–51 (2007).
  • Izumi Y, Xu L, di Tomaso E, Fukumura D, Jain RK. Tumour biology: Herceptin acts as an anti-angiogenic cocktail. Nature416(6878), 279–280 (2002).
  • Alinari L, Lapalombella R, Andritsos L, Baiocchi RA, Lin TS, Byrd JC. Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia. Oncogene26(25), 3644–3653 (2007).
  • Hale G, Dyer MJ, Clark MR et al. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet2(8625), 1394–1399 (1988).
  • Ravandi F, O’Brien S. Alemtuzumab. Expert Rev. Anticancer Ther.5(1), 39–51 (2005).
  • Galizia G, Lieto E, De Vita F et al. Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer. Oncogene26(25), 3654–3660 (2007).
  • Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H. Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int. J. Cancer120(4), 781–787 (2007).
  • Mendelsohn J. Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. Clin. Cancer Res.3(12 Pt 2), 2703–2707 (1997).
  • Kim KJ, Li B, Winer J et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature362(6423), 841–844 (1993).
  • Kramer I, Lipp HP. Bevacizumab, a humanized anti-angiogenic monoclonal antibody for the treatment of colorectal cancer. J. Clin. Pharm Ther.32(1), 1–14 (2007).
  • Presta LG, Chen H, O’Connor SJ et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res.57(20), 4593–4599 (1997).
  • Cohenuram M, Saif MW. Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anticancer Drugs18(1), 7–15 (2007).
  • Jakobovits A, Amado RG, Yang X, Roskos L, Schwab G. From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice. Nat. Biotechnol.25(10), 1134–1143 (2007).
  • Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat. Med.6(4), 443–446 (2000).
  • Fan Z, Masui H, Altas I, Mendelsohn J. Blockade of epidermal growth factor receptor function by bivalent and monovalent fragments of 225 anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res.53(18), 4322–4328 (1993).
  • Desjarlais JR, Lazar GA, Zhukovsky EA, Chu SY. Optimizing engagement of the immune system by anti-tumor antibodies: an engineer’s perspective. Drug Discov. Today12(21–22), 898–910 (2007).
  • Clynes R. Antitumor antibodies in the treatment of cancer: Fc receptors link opsonic antibody with cellular immunity. Hematol. Oncol. Clin. North Am.20(3), 585–612 (2006).
  • Nimmerjahn F, Ravetch JV. Fcγ receptors: old friends and new family members. Immunity24(1), 19–28 (2006).
  • Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Kohl J. The role of the anaphylatoxins in health and disease. Mol. Immunol.46(14), 2753–2766 (2009).
  • Regnault A, Lankar D, Lacabanne V et al. Fcγ receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J. Exp. Med.189(2), 371–380 (1999).
  • Boruchov AM, Heller G, Veri MC, Bonvini E, Ravetch JV, Young JW. Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J. Clin. Invest.115(10), 2914–2923 (2005).
  • Schakel K, Mayer E, Federle C, Schmitz M, Riethmuller G, Rieber EP. A novel dendritic cell population in human blood: one-step immunomagnetic isolation by a specific mAb (M-DC8) and in vitro priming of cytotoxic T lymphocytes. Eur. J. Immunol.28(12), 4084–4093 (1998).
  • Abes R, Gelize E, Fridman WH, Teillaud JL. Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response. Blood116(6), 926–934 (2010).
  • Selenko N, Majdic O, Jager U, Sillaber C, Stockl J, Knapp W. Cross-priming of cytotoxic T cells promoted by apoptosis-inducing tumor cell reactive antibodies? J. Clin. Immunol.22(3), 124–130 (2002).
  • Taylor C, Hershman D, Shah N et al. Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy. Clin. Cancer Res.13(17), 5133–5143 (2007).
  • Horlock C, Stott B, Dyson PJ et al. The effects of trastuzumab on the CD4+CD25+FOXP3+ and CD4+IL17A+ T-cell axis in patients with breast cancer. Br. J. Cancer100(7), 1061–1067 (2009).
  • Park S, Jiang Z, Mortenson ED et al. The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell18(2), 160–170.
  • Gilboa E. DC-based cancer vaccines. J. Clin. Invest.117(5), 1195–1203 (2007).
  • Schadendorf D, Ugurel S, Schuler-Thurner B et al. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized Phase III trial of the DC study group of the DeCOG. Ann. Oncol.17(4), 563–570 (2006).
  • Small EJ, Schellhammer PF, Higano CS et al. Placebo-controlled Phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J. Clin. Oncol.24(19), 3089–3094 (2006).
  • Dhodapkar KM, Kaufman JL, Ehlers M et al. Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells. Proc. Natl Acad. Sci. USA102(8), 2910–2915 (2005).
  • Kalergis AM, Ravetch JV. Inducing tumor immunity through the selective engagement of activating Fcγ receptors on dendritic cells. J. Exp. Med.195(12), 1653–1659 (2002).
  • Akiyama K, Ebihara S, Yada A et al. Targeting apoptotic tumor cells to Fc γ R provides efficient and versatile vaccination against tumors by dendritic cells. J. Immunol.170(4), 1641–1648 (2003).
  • Rafiq K, Bergtold A, Clynes R. Immune complex-mediated antigen presentation induces tumor immunity. J. Clin. Invest.110(1), 71–79 (2002).
  • You Z, Huang X, Hester J, Toh HC, Chen SY. Targeting dendritic cells to enhance DNA vaccine potency. Cancer Res.61(9), 3704–3711 (2001).
  • Qin H, Zhou C, Wang D et al. Specific antitumor immune response induced by a novel DNA vaccine composed of multiple CTL and T helper cell epitopes of prostate cancer associated antigens. Immunol. Lett.99(1), 85–93 (2005).
  • Harbers SO, Crocker A, Catalano G et al. Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance. J. Clin. Invest.117(5), 1361–1369 (2007).
  • Kim PS, Armstrong TD, Song H et al. Antibody association with HER-2/neu-targeted vaccine enhances CD8 T cell responses in mice through Fc-mediated activation of DCs. J. Clin. Invest.118(5), 1700–1711 (2008).
  • Saenger YM, Li Y, Chiou KC et al. Improved tumor immunity using anti-tyrosinase related protein-1 monoclonal antibody combined with DNA vaccines in murine melanoma. Cancer Res.68(23), 9884–9891 (2008).
  • Weiner LM, Dhodapkar MV, Ferrone S. Monoclonal antibodies for cancer immunotherapy. Lancet373(9668), 1033–1040 (2009).
  • Pfisterer J, du Bois A, Sehouli J et al. The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A Phase I trial of the AGO-OVAR. Ann. Oncol.17(10), 1568–1577 (2006).
  • Reinartz S, Kohler S, Schlebusch H et al. Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (Phase Ib/II). Clin. Cancer Res.10(5), 1580–1587 (2004).
  • Sabbatini P, Dupont J, Aghajanian C et al. Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Clin. Cancer Res.12(18), 5503–5510 (2006).
  • Wagner U, Kohler S, Reinartz S et al. Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clin. Cancer Res.7:1112–1115, 2001. Clin. Cancer Res.7(5), 1154–1162 (2001).
  • Diaz Y, Gonzalez A, Lopez A, Perez R, Vazquez AM, Montero E. Anti-ganglioside anti-idiotypic monoclonal antibody-based cancer vaccine induces apoptosis and antiangiogenic effect in a metastatic lung carcinoma. Cancer Immunol. Immunother.58(7), 1117–1128 (2009).
  • Amin S, Robins RA, Maxwell-Armstrong CA, Scholefield JH, Durrant LG. Vaccine-induced apoptosis: a novel clinical trial end point? Cancer Res.60(12), 3132–3136 (2000).
  • Pritchard-Jones K, Wilton C, Spendlove I et al. Immune responses to the 105AD7 human anti-idiotypic vaccine after intensive chemotherapy for osteosarcoma. 92(8), 1358–1365 (2005).
  • Ullenhag GJ, Mukherjee A, Watson NF, Al-Attar AH, Scholefield JH, Durrant LG. Overexpression of FLIPL is an independent marker of poor prognosis in colorectal cancer patients. Clin. Cancer Res.13(17), 5070–5075 (2007).
  • Ullenhag GJ, Spendlove I, Watson NF, Kallmeyer C, Pritchard-Jones K, Durrant LG. T-cell responses in osteosarcoma patients vaccinated with an anti-idiotypic antibody, 105AD7, mimicking CD55. Clin. Immunol.128(2), 148–154 (2008).
  • Billetta R, Hollingdale MR, Zanetti M. Immunogenicity of an engineered internal image antibody. Proc. Natl Acad. Sci. USA88(11), 4713–4717 (1991).
  • Brumeanu TD, Swiggard WJ, Steinman RM, Bona CA, Zaghouani H. Efficient loading of identical viral peptide onto class II molecules by antigenized immunoglobulin and influenza virus. J. Exp. Med.178(5), 1795–1799 (1993).
  • Li S, Polonis V, Isobe H et al. Chimeric influenza virus induces neutralizing antibodies and cytotoxic T cells against human immunodeficiency virus type 1. J. Virol.67(11), 6659–6666 (1993).
  • Kuzu Y, Kuzu H, Zaghouani H, Bona C. Priming of cytotoxic T lymphocytes at various stages of ontogeny with transfectoma cells expressing a chimeric Ig heavy chain gene bearing an influenza virus nucleoprotein peptide. Int. Immunol.5(10), 1301–1307 (1993).
  • Zaghouani H, Steinman R, Nonacs R, Shah H, Gerhard W, Bona C. Presentation of a viral T cell epitope expressed in the CDR3 region of a self immunoglobulin molecule. Science259(5092), 224–227 (1993).
  • Bot A, Smith D, Phillips B, Bot S, Bona C, Zaghouani H. Immunologic control of tumors by in vivo Fc γ receptor-targeted antigen loading in conjunction with double-stranded RNA-mediated immune modulation. J. Immunol.176(3), 1363–1374 (2006).
  • Metheringham RL, Pudney VA, Gunn B, Towey M, Spendlove I, Durrant LG. Antibodies designed as effective cancer vaccines. MABs1(1), 71–85 (2009).
  • Pudney VA, Metheringham RL, Gunn B, Spendlove I, Ramage JM, Durrant LG. DNA vaccination with T-cell epitopes encoded within Ab molecules induces high-avidity anti-tumor CD8+ T cells. Eur. J. Immunol.40(3), 899–910 (2010).
  • Fuller DH, Loudon P, Schmaljohn C. Preclinical and clinical progress of particle-mediated DNA vaccines for infectious diseases. Methods40(1), 86–97 (2006).
  • Ahlen G, Soderholm J, Tjelle T et al.In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells. J. Immunol.179(7), 4741–4753 (2007).
  • van Drunen Littel-van den Hurk S, Lawman Z, Wilson D et al. Electroporation enhances immune responses and protection induced by a bovine viral diarrhea virus DNA vaccine in newborn calves with maternal antibodies. Vaccine28(39), 6445–6454 (2010).
  • Fredriksen AB, Sandlie I, Bogen B. DNA vaccines increase immunogenicity of idiotypic tumor antigen by targeting novel fusion proteins to antigen-presenting cells. Mol. Ther.13(4), 776–785 (2006).
  • Tunheim G, Thompson KM, Fredriksen AB, Espevik T, Schjetne KW, Bogen B. Human receptors of innate immunity (CD14, TLR2) are promising targets for novel recombinant immunoglobulin-based vaccine candidates. Vaccine25(24), 4723–4734 (2007).
  • Hawiger D, Inaba K, Dorsett Y et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med.194(6), 769–779 (2001).
  • Mahnke K, Qian Y, Fondel S, Brueck J, Becker C, Enk AH. Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice. Cancer Res.65(15), 7007–7012 (2005).
  • Charalambous A, Oks M, Nchinda G, Yamazaki S, Steinman RM. Dendritic cell targeting of survivin protein in a xenogeneic form elicits strong CD4+ T cell immunity to mouse survivin. J. Immunol.177(12), 8410–8421 (2006).
  • Idoyaga J, Cheong C, Suda K et al. Cutting edge: langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo. J. Immunol.180(6), 3647–3650 (2008).
  • Demangel C, Zhou J, Choo AB, Shoebridge G, Halliday GM, Britton WJ. Single chain antibody fragments for the selective targeting of antigens to dendritic cells. Mol. Immunol.42(8), 979–985 (2005).
  • Nchinda G, Kuroiwa J, Oks M et al. The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells. J. Clin. Invest.118(4), 1427–1436 (2008).
  • Grossmann C, Tenbusch M, Nchinda G et al. Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic Toll-like receptor ligands. BMC Immunol.10, 43 (2009).
  • Ramakrishna V, Treml JF, Vitale L et al. Mannose receptor targeting of tumor antigen pmel17 to human dendritic cells directs anti-melanoma T cell responses via multiple HLA molecules. J. Immunol.172(5), 2845–2852 (2004).
  • He LZ, Crocker A, Lee J et al. Antigenic targeting of the human mannose receptor induces tumor immunity. J. Immunol.178(10), 6259–6267 (2007).
  • Luhder F, Huang Y, Dennehy KM et al. Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists. J. Exp. Med.197(8), 955–966 (2003).
  • Rodriguez-Palmero M, Hara T, Thumbs A, Hunig T. Triggering of T cell proliferation through CD28 induces GATA-3 and promotes T helper type 2 differentiation in vitro and in vivo. Eur. J. Immunol.29(12), 3914–3924 (1999).
  • Suntharalingam G, Perry MR, Ward S et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N. Engl. J. Med.355(10), 1018–1028 (2006).
  • Alegre ML, Noel PJ, Eisfelder BJ et al. Regulation of surface and intracellular expression of CTLA4 on mouse T cells. J. Immunol.157(11), 4762–4770 (1996).
  • Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity4(6), 535–543 (1996).
  • van der Merwe PA, Bodian DL, Daenke S, Linsley P, Davis SJ. CD80 (B7–1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics. J. Exp. Med.185(3), 393–403 (1997).
  • Chambers CA, Sullivan TJ, Truong T, Allison JP. Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells. Eur. J. Immunol.28(10), 3137–3143 (1998).
  • Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity3(5), 541–547 (1995).
  • Waterhouse P, Penninger JM, Timms E et al. Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science270(5238), 985–988 (1995).
  • Morse MA. Technology evaluation: ipilimumab, Medarex/Bristol-Myers Squibb. Curr. Opin. Mol. Ther.7(6), 588–597 (2005).
  • Read S, Greenwald R, Izcue A et al. Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo. J. Immunol.177(7), 4376–4383 (2006).
  • Sansom DM, Walker LS. The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology. Immunol. Rev.212, 131–148 (2006).
  • Takahashi T, Tagami T, Yamazaki S et al. Immunologic self-tolerance maintained by CD25+ CD4+ regulatory T Cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med.192(2), 303–309 (2000).
  • Grohmann U, Orabona C, Fallarino F et al. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat. Immunol.3(11), 1097–1101 (2002).
  • Ying H, Yang L, Qiao G et al. Cutting edge: CTLA-4–B7 interaction suppresses Th17 cell differentiation. J. Immunol.185(3), 1375–1378 (2010).
  • Kwon ED, Hurwitz AA, Foster BA et al. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc. Natl Acad. Sci. USA94(15), 8099–8103 (1997).
  • Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science271(5256), 1734–1736 (1996).
  • Yang YF, Zou JP, Mu J et al. Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumor-bearing stages. Cancer Res.57(18), 4036–4041 (1997).
  • Sutmuller RP, van Duivenvoorde LM, van Elsas A et al. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J. Exp. Med.194(6), 823–832 (2001).
  • Hurwitz AA, Foster BA, Kwon ED et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res.60(9), 2444–2448 (2000).
  • Hurwitz AA, Yu TF, Leach DR, Allison JP. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc. Natl Acad. Sci. USA95(17), 10067–10071 (1998).
  • van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med.190(3), 355–366 (1999).
  • Quezada SA, Peggs KS, Curran MA, Allison JP. CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J. Clin. Invest.116(7), 1935–1945 (2006).
  • Quezada SA, Simpson TR, Peggs KS et al. Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J. Exp. Med.207(3), 637–650 (2010).
  • Camacho LH, Antonia S, Sosman J et al. Phase I/II trial of tremelimumab in patients with metastatic melanoma. J. Clin. Oncol.27(7), 1075–1081 (2009).
  • Robert C, Ghiringhelli F. What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma? Oncologist14(8), 848–861 (2009).
  • Hodi FS, O’Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med.363(8), 711–723 (2010).
  • Maker AV, Attia P, Rosenberg SA. Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with CTLA-4 blockade. J. Immunol.175(11), 7746–7754 (2005).
  • Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol.26, 677–704 (2008).
  • Nishimura H, Okazaki T, Tanaka Y et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science291(5502), 319–322 (2001).
  • Nishimura T, Iwakabe K, Sekimoto M et al. Distinct role of antigen-specific T helper type 1 (Th1) and Th2 cells in tumor eradication in vivo. J. Exp. Med.190(5), 617–627 (1999).
  • Hamanishi J, Mandai M, Iwasaki M et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc. Natl Acad. Sci. USA104(9), 3360–3365 (2007).
  • Thompson RH, Kuntz SM, Leibovich BC et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res.66(7), 3381–3385 (2006).
  • Blank C, Brown I, Marks R, Nishimura H, Honjo T, Gajewski TF. Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells. J. Immunol.171(9), 4574–4581 (2003).
  • Keir ME, Freeman GJ, Sharpe AH. PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues. J. Immunol.179(8), 5064–5070 (2007).
  • Ansari MJ, Salama AD, Chitnis T et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J. Exp. Med.198(1), 63–69 (2003).
  • Keir ME, Liang SC, Guleria I et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J. Exp. Med.203(4), 883–895 (2006).
  • Probst HC, McCoy K, Okazaki T, Honjo T, van den Broek M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat. Immunol.6(3), 280–286 (2005).
  • Francisco LM, Salinas VH, Brown KE et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J. Exp. Med.206(13), 3015–3029 (2009).
  • Latchman Y, Wood CR, Chernova T et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol.2(3), 261–268 (2001).
  • Parry RV, Chemnitz JM, Frauwirth KA et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell Biol.25(21), 9543–9553 (2005).
  • Barber DL, Wherry EJ, Masopust D et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature439(7077), 682–687 (2006).
  • Fourcade J, Kudela P, Sun Z et al. PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients. J. Immunol.182(9), 5240–5249 (2009).
  • Wong RM, Scotland RR, Lau RL et al. Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int. Immunol.19(10), 1223–1234 (2007).
  • Blank C, Brown I, Peterson AC et al. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res.64(3), 1140–1145 (2004).
  • Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl Acad. Sci. USA99(19), 12293–12297 (2002).
  • Strome SE, Dong H, Tamura H et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res.63(19), 6501–6505 (2003).
  • Brahmer JR, Drake CG, Wollner I et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol.28(19), 3167–3175 (2010).
  • Brahmer JR, Toplian SL, Powderly J et al. Phase II experience with MDX-1106 (ONO-4538), an anti-PD-1/PD-L1 monoclonal antibody, in patients with selected refractory or relapsed malignancies. J. Clin. Oncol.27 (2008) (Abstract 3015).
  • Berger R, Rotem-Yehudar R, Slama G et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin. Cancer Res.14(10), 3044–3051 (2008).
  • Schuurhuis DH, Laban S, Toes RE et al. Immature dendritic cells acquire CD8(+) cytotoxic T lymphocyte priming capacity upon activation by T helper cell-independent or -dependent stimuli. J. Exp. Med.192(1), 145–150 (2000).
  • Diehl L, den Boer AT, Schoenberger SP et al. CD40 activation in vivo overcomes peptide-induced peripheral cytotoxic T-lymphocyte tolerance and augments anti-tumor vaccine efficacy. Nat. Med.5(7), 774–779 (1999).
  • van Mierlo GJ, Boonman ZF, Dumortier HM et al. Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication. J. Immunol.173(11), 6753–6759 (2004).
  • Vonderheide RH, Flaherty KT, Khalil M 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(7), 876–883 (2007).
  • Advani R, Forero-Torres A, Furman RR et al. Phase I study of the humanized anti-CD40 monoclonal antibody dacetuzumab in refractory or recurrent non-Hodgkin’s lymphoma. J. Clin. Oncol.27(26), 4371–4377 (2009).
  • Weinberg AD, Evans DE, Thalhofer C, Shi T, Prell RA. The generation of T cell memory: a review describing the molecular and cellular events following OX40 (CD134) engagement. J. Leukoc. Biol.75(6), 962–972 (2004).
  • Evans DE, Prell RA, Thalhofer CJ, Hurwitz AA, Weinberg AD. Engagement of OX40 enhances antigen-specific CD4(+) T cell mobilization/memory development and humoral immunity: comparison of αOX-40 with αCTLA-4. J. Immunol.167(12), 6804–6811 (2001).
  • Kjaergaard J, Tanaka J, Kim JA, Rothchild K, Weinberg A, Shu S. Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res.60(19), 5514–5521 (2000).
  • Redmond WL, Gough MJ, Charbonneau B, Ratliff TL, Weinberg AD. Defects in the acquisition of CD8 T cell effector function after priming with tumor or soluble antigen can be overcome by the addition of an OX40 agonist. J. Immunol.179(11), 7244–7253 (2007).
  • Weinberg AD, Rivera MM, Prell R et al. Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J. Immunol.164(4), 2160–2169 (2000).
  • Kovacsovics-Bankowski M WE, Floyd k et al. Increased CD4 and CD8 memory T cell proliferation following anti-OX40 administration to cancer patients: immunologic assessment of a Phase I clinical trial. Curr. Opin. Oncol.23(2), 163–169 (2009).
  • Alderson MR, Smith CA, Tough TW et al. Molecular and biological characterization of human 4-1BB and its ligand. Eur. J. Immunol.24(9), 2219–2227 (1994).
  • Gramaglia I, Cooper D, Miner KT, Kwon BS, Croft M. Co-stimulation of antigen-specific CD4 T cells by 4-1BB ligand. Eur. J. Immunol.30(2), 392–402 (2000).
  • Shuford WW, Klussman K, Tritchler DD et al. 4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J. Exp. Med.186(1), 47–55 (1997).
  • Miller RE, Jones J, Le T et al. 4-1BB-specific monoclonal antibody promotes the generation of tumor-specific immune responses by direct activation of CD8 T cells in a CD40-dependent manner. J. Immunol.169(4), 1792–1800 (2002).
  • Sznol M, Hodi FS, Margolin K et al. Phase I study of BMS-663513, a fully human anti-CD137 agonist monoclonal antibody, in patients (pts) with advanced cancer. J. Clin. Oncol.26(Suppl.), (2008) (Abstract 3007).

Website

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.