The therapeutic potential of 4-1BB (CD137) in cancer

Current Cancer Drug Targets

Volumn 5, Issue 5, 2005, Pages 357-363

  Nam, Kyung Ok ^b   Kang, Woo Jin ^b   Kwon, Byoung S ^b   Kim, Sung Jin ^a   Lee, Hyeon Woo ^a  

^a Kyung Hee University   (South Korea)

^b University of Ulsan   (South Korea)

Author keywords

4 1BB; Cancer; CD8+ T cells; Signaling pathways

Indexed keywords

CD137 LIGAND; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY CD137 LIGAND; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; CANCER; CANCER IMMUNOTHERAPY; CROSS LINKING; DENDRITIC CELL; HUMAN; IMMUNOSTIMULATION; IN VITRO STUDY; IN VIVO STUDY; NATURAL KILLER CELL; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD; ANTIGENS, CD137; ANTINEOPLASTIC AGENTS; CD8-POSITIVE T-LYMPHOCYTES; HUMANS; IMMUNOTHERAPY; LYMPHOCYTE ACTIVATION; NEOPLASMS; RECEPTORS, NERVE GROWTH FACTOR; RECEPTORS, TUMOR NECROSIS FACTOR; SIGNAL TRANSDUCTION; T-LYMPHOCYTE SUBSETS;

EID: 23244437934     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/1568009054629681     Document Type: Review

References (86)

1. Abbas, A. K.; Lichtman, A. H. Cellular and Molecular Immunology; Jason Malley, Ed.; Elsevier Science USA: Philadelphia, Pennsylvania, 2003, pp. 298-317.
2. Carreno, B. M.; Collins, M. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Annu. Rev. Immunol. 2002, 20, 29-53.
3. Chambers, C. A.; Allison, J. P. Costimulatory regulation of T cell function. Curr. Opin. Cell Biol. 1999, 11, 203-210.
4. + T cells. Pathologie Biologie 2003, 51, 64-66.
5. Nakajima, H.; Shores, E. W.; Noguchi, M.; Leonard, W. J. The common cytokine receptor gamma chain plays an essential role in regulating lymphoid homeostasis. J. Exp. Med. 1997, 185, 189-195.
6. + T cell survival but not for antigen proliferation. Nat. Immunol. 2000, 1, 54-58.
7. Unutmaz, D.; Pileri, P.; Abrignani, S. Antigen-independent activation of naïve and memory resting T cell by a cytokine combination. J. Exp. Med. 1994, 180, 1159-1164.
8. Unutmaz, D.; Baldoni, F.; Abrignani, S. Human naïve T Cells activated by cytokines differentiate into a split phenotype with functional features intermediate between naïve and memory T cells. Int. Immunol. 1995, 7, 1417-1424.
9. Kanegane, H.; Tosato, G. Activation of naïve and memory T cells by interleukin-15. Blood 1996, 88, 230-235.
10. Zhang, X.; Sun, S.; Hwang, I.; Tough, D. F.; Sprent, J. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 1998, 8, 591-599.
11. Lodolce, J. P.; Boone, D. L.; Chai, S.; Swain, R. E.; Dassopoulos, T.; Trettin, S.; Ma, A. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 1998, 9, 669-676.
12. Schluns, K. S.; Kieper, W. C.; Jameson, S. C.; Lefrancois, L. Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo. Nat. Immunol. 2000, 1, 426-432.
13. Samia, J. K.; Mohamed, H. S. The Roles of the New Negative T cell Costimulatory Pathways in Regulating Autoimmunity. Immunity 2004, 20, 529-538.
14. Van Parijs, L.; Abbas, A. K. Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 1998, 280, 243-248.
15. Rothstein, D. M.; Sayegh, M. H. T-cell costimulatory pathways in allograft rejection and tolerance. Immunol. Rev. 2003, 196, 85-108.
16. Kenneth, A. T.; Thompson, C. B. Activation and Inhibition of lymphocytes by costimulation. J. Clin. Invest. 2002, 109, 295-299.
17. Gravestein, L. A.; Amsen, D.; Boes, M.; Calvo, C. R.; Kruisbeek, A. M.; Borst, J. The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2. Eur. J. Immunol. 1998, 28, 2208-2216.
18. Michael, C. Costimulation of T cells by OX40, 4-1BB, and CD27. Cytokine Growth Factor Rev. 2003, 14, 265-273.
19. June, C. H.; Ledbetter, J. A.; Linsley, P. S.; Thompson, C. B. Role of the CD28 receptor in T-cell activation. Immunol. Today 1990, 11, 211-216.
20. Watts, T. H.; DeBenedette, M. A. T cell co-stimulatory molecules other than CD28. Curr. Opin. Immunol. 1999, 11, 286-293.
21. Mueller, D. L. T cell: a proliferation of costimulatory molecules. Curr. Biol. 2000, 10, R227-R230.
22. Lenschow, D. J.; Walunas, T. L.; Bluestone, J. A. CD28/B7 system of T cell costimulation. Annu. Rev. Immunol. 1996, 14, 233-258.
23. Okkenhaung, K.; Wu, L.; Garza, K. M.; La Rose, J.; Khoo, W.; Odermatt, B.; Mak, T. K. A point mutation in CD28 distinguishes proliferative signals from survival signals. Nat. Immunol. 2001, 2, 325-332.
24. Mueller, D. L.; Jenkins, M. K.; Schwarz, R. H. Clonal expansion versus functional clonal inactivation: a costimulatory signaling pathway determines the outcome of T cell antigen receptor occupancy. Annu. Rev. Immunol. 1989, 7, 445-480.
25. Weinberg, A. D.; Vella, A. T.; Croft, M. Ox-40: life beyond the effector T cell stage. Semin. Immunol. 1998, 10, 471-480.
26. Watts, T. H.; DeBenedette, M. A. T cell costimulatory molecule other than CD28. Curr. Opin. Immunol. 1999, 11, 286-293.
27. Gravestein, L. A.; Borst, J. Tumor necrosis factor receptor family members in the immune system. Semin. Immunol. 1998, 10, 423-434.
28. Kwon, B. S.; Weissman, S. M. cDNA sequences of two inducible T-cell genes. Proc. Natl. Acad. Sci. USA 1989, 86, 1963-1967.
29. Schwarz H.; Tuckwell, J.; Lotz, M. A receptor-induced by lymphocyte activation (ILA): a new member of the human nerve growth factor/tumor necrosis factor receptor family. Gene 1993, 134, 295-298.
30. Melero, I.; Shuford, W. W.; Newby, S. A.; Aruffo, A.; Ledbetter, J. A.; Hellstrom, K. E.; Mittler, R. S.; Chen, L. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat. Med. 1997, 3, 682-685.
31. Futagawa, T.; Akiba, H.; Kodama, T.; Takeda, K.; Hosoda, Y.; Yagita, H. Expression and function of 4-1BB and 4-1BB ligand on murine dendrine dendritic cells. Int. Immunol. 2002, 14, 275-286.
32. Wilcox, R. A.; Chapoval, A. I.; Gorski, K. S.; Otsuji, M.; Shin, T.; Flies, D. B.; Tamada, K.; Mittler, R. S.; Tsuchiya, H.; Pardoll, D. M.; Chen, L. Cutting edge: Expression of functional CD137 receptor by dendritic cells. J. Immunol. 2002, 168, 4262-4267.
33. Kwon, B.; Lee, H. W.; Kwon, B. S. New insights into the role of 4-1BB in immune response: beyond CD8+ T cells. TRENDS in Immunol. 2002, 23, 378-380.
34. Pan, P. Y.; Gu, P.; Li, Q.; Xu, D.; Weber, K.; Chen, S. H. Regulation of Dendritic Cell Function by NK Cell: Mechanisms Underlying the Synergism in the Combination Therapy of IL-12 and 4-1BB Activation. J. Immunol. 2004, 172, 4779-4789.
35. Zheng, G.; Wang, B.; Chen, A. The 4-1BB Costimulation Augments the Proliferation of CD4+CD25+ Regulatory T Cell. J. Immunol. 2004, 173, 2428-2434.
36. Choi, B. K.; Bae, J. S.; Choi, E. M.; Kang, W. J.; Sakaguchi, S.; Vinay, D. S.; Kwon, B. S. 4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cell. J. Leukoc. Biol. 2004, 75, 785-791.
37. Vinay, D. S.; Kwon, B. S. Role of 4-1BB in immune response. Semin. Immunol. 1998, 10, 481-489.
38. Kwon, B.; Moon, C. H.; Seo, S. K.; Kwon, B. S. 4-1BB: still in the midst of darkness. Mol. Cells 2000, 30, 119-126.
39. Shuford, W. W.; Klussman, K.; Tritchler, D. D.; Loo, D. T.; Chalupny, J.; Siadak, A. W.; Brown, T. J.; Emswiler, J.; Raecho, H.; Larsen, C. P.; Pearson, T. C.; Ledbetter, J. A.; Aruffo, A.; Mittler. R. S. 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. 1997, 186, 47-55.
40. Tan, J. T.; Ha, J.; Cho, H. R.; Tucker-Burden C.; Hendrix, R. C.; Mittler, R. S.; Pearson, T. C.; Larsen, C. P. Analysis of expression and function of the costimulatory molecule 4-1BB in alloimmune responses. Transplantation 2000, 70, 175-183.
41. Bertram, E. M.; Lau, P.; Watts, T. H. Temporal Segregation of 4-1BB versus CD28-Mediated Costimulation: 4-1BB Ligand Influenes T cell Numbers Late in the Primary Response and Regulates the Size of the T Cell Memory response Following Influenza Infection. J. Immunol. 2002, 168, 3777-3785.
42. L and Bfl-1. J. Immunol. 2002, 169, 4882-4888.
43. kip1. Eur. J. Immunol. 2003, 33, 2133-2141.
44. Kim, Y. J.; Brutkiewicz, R. R.; Broxmeyer, H. E. Role of 4-1BB (CD137) in the functional activation of cord blood. Blood 2002, 100, 3253-3260.
45. Seo, S. K.; Choi, J. H.; Kim, Y. H.; Kang, W. J.; Suh, J. H.; Choi, B. K.; Vinay, D. S.; Kwon, B. S. 4-1BB-mediated immunotherapy of rheumatoid arthritis. Nat. Med 2004, 10, 1088-1094.
46. Brennan, P.; Babbage, J. W.; Burgering, B. M. T.; Groner, B.; Reif, K.; Cantrell, D. A. Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Immunity 1997, 7, 679-689.
47. Moon, J. J.; Nelson, B. H. Phosphatidylinositol 3-kinase potentiates, but does not trigger, T cell proliferation mediated by the IL-2 receptor. J. Immunol. 2001, 167, 2714-2723.
48. Kuo, C. J.; Chung, J.; Fiorentino, D. F.; Flanagan, W. M.; Blenis, J.; Crabtree, G. R. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature 1992, 355, 70-73.
49. Gingras, A.-C.; Raught, B.; Sonenberg, N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001, 15, 807-826.
50. Jang, I. K.; Lee, Z. H.; Kim, Y.-J.; Kwon, B. S. Human 4-1BB (CD 137) signals are mediated by TRAF2 and activate nuclear factor-κB. Biophys. Biochem. Res. Commun. 1998, 242, 613-620.
51. Arch, R. H.; Thompson, C. B. 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor κB. Mol. Cell. Biol. 1998, 18, 558-565.
52. Saoulli, K.; Lee, S. Y.; Cannons, J. L.; Yeh, W. C.; Santana, A.; Goldstein, M. D.; Bangia, N.; DeBenedette, M. A.; Mak, T. W.; Choi, Y.; Watts, T. H. CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand. J. Exp. Med. 1998, 187, 1849-1862.
53. Cannons, J. L.; Choi, Y.; Watts, T. H. Role of TNF receptor-associated factor 2 and p38 mitogen-activated protein kinase activation during 4-1BB-dependent immune response. J. Immunol. 2000, 165, 6193-6204.
54. Nam, K. O.; Kang, H.; Shin, S. M.; Kim, S. J.; Cho, K. H.; Kwon, B. S.; Lee, H. W. Cross-linking of 4-1BB activates TCR signaling pathways in CD8+ T lymphocytes. J. Immunol. 2005, 174, 1898-1905.
55. Hellstrom, K. E.; Hellstrom I. Therapeutic vaccination with tumor cells that engage CD137. J. Mol. Med. 2003, 81, 71-86.
56. Hellstrom, K. E.; Hellstrom, I. In Cancer Vaccines: Handbook of experimental pharmacology; Perlmann, P.; Wigzell, H., Eds.; Springer, Berlin Heigelberg, NY, 1999.
57. Kiessling, R.; Wasserman, K.; Horiguchi, S.; Kono, K.; Sjoberg, J.; Pisa, P.; Petersson, M. Tumor-induced immune dysfunction. Cancer Immunol. Immunother. 1999, 48, 353-362.
58. Murillo, O.; Arina, A.; Tirapu, I.; Alfaro, C.; Mazzolini, G.; Palencia, B.; Cerio, A. L.; Prieto, J.; Bendandi, M.; Melero I. Potentiation of Therapeutic Immune Responses against Malignancies with Monoclonal Antibodies. Clin. Cancer Res. 2003, 9, 5454-5464.
59. Cella, M.; Scheigegger, D.; Palmer-Lehmann, K.; Lane, P.; Lanzavecchia, A.; Alber, G. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med. 1996, 184, 747-752.
60. Egen, J. G.; Kuhns, M. S.; Allison, J. P. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat. Immunol. 2002, 2, 116-126.
61. Sharpe, A. H.; Freeman, G. J. The B7-CD28 superfamily. Nat. Rev. Immunol. 2002, 2, 116-126.
62. Lee, S. J.; Myers, L.; Muralimohan, G.; Gai, J.; Qiao, Y.; Li, Z.; Mittler, R. S.; Vella, A. T. 4-1BB and OX40 dual costimulation synergistically stimulate primary specific CD8 T cells for robust effector function. J. Immunol. 2004, 173, 3002-3012.
63. Guinn, B. A.; DeBenedette, M. A.; Watts, T. H.; Berinstein, N. L. 4-1BBL cooperates with B7-1 and B7-2 in converting a B cell lymphoma cell line into a long-lasting antitumor vaccine. J. Immunol. 1999, 162, 5003-5010.
64. Lee, H.-W.; Nam, K.-O.; Seo, S. K.; Kim, Y. H.; Kang, H.; Kwon, B. S. 4-1BB cross-linking enhances the survival and cell cycle progression of CD4 T lymphocytes. Cell. Immunol. 2003, 223, 143-150.
65. Wiethe, C.; Dittmar, K.; Doan, T.; Lindenmaier, W.; Tindle, R. Provision of 4-1BB ligand enhances effector and memory CTL responses generated by immunization with dendritic cells expressing a human tumor-associated antigen. J. Immunol. 2003, 170, 2912-2922.
66. Sun, Y.; Lin, X.; Chen, H. M.; Wu, Q.; Sumit, K.; Subudhi, S. K.; Chen, L. Fu, Y. X. Administration of Agonistic Anti-4-1BB Monoclonal Antibody leads to the Amelioration of Experimental Autoimmune Encephalomyelitis. J. Immunol. 2002, 168, 1457-1465.
67. Sun, Y.; Chen, H. M.; Sumit, K.; Subudhi, S. K.; Chen, J.; Koka, R.; Chen, L.; Fu, Y. X. Costimulatory molecule-targeted antibody therapy of a a spontaneous autoimmune disease. Nat. Med. 2002, 8, 1405-1413.
68. Seo, S. K.; Choi, J. H.; Kim, Y. H.; Kang, W. J.; Park, H. Y.; Suh, J. H.; Choi, B. K.; Vinay, D. S.; Kwon, B. S. 4-1BB-mediated immunotherapy of rheumatoid arthritis. Nat. Med. 2004, 10, 1088-1094.
69. Kim, J. Y.; Choi, W. S.; La, S. J.; Suh, J. H.; Kim, B. S.; Cho, H. R.; Kwon, B. S.; Kwon, B. Stimulation with 4-1BB (CD137) inhibits chronic graft-versus-host disease by inducing activation-induced cell death of donor CD4+ T cells. Blood 2005, 105, 2206-2213.
70. Kim, J. A.; Averbook, B. J.; Chambers, K.; Rothchild, K.; Kiaergaard, J.; Papay, R.; Shu, S. Divergent effects of 4-1BB antibodies on antitumor immunity and on tumor-reactive T-cell generation. Cancer Res. 2001, 61, 2031-2037.
71. Yang, S.; Yang, Y.; Raycraft, J.; Zhang, H.; Kanan, S.; Guo, Y.; Ronai, Z.; Hellstrom, I.; Hellstrom, K. E. Melanoma cells transfectied to express CD83 induce antitumor immunity that can be increased by also engaging CD137. Proc. Natl. Acd. Sci. USA 2004, 101, 4990-4995.
72. Kienzle, G.; kempis, J. V. CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes. Int. Immunol. 2000, 12, 73-82.
73. Isabelle, B. W. M. H.; Isabelle, D.; Bruno, K.; Simon, J. U. CD137 activation abrogates granulocyte-macrophage colony-stimulating factor-mediated anti-apoptosis in neutrophils. Eur. J. Immunol. 2000, 30, 3441-3446.
74. Pauly, S.; Broll, K.; Wittmann, M.; Giegerich, G.; Schwarz, H. CD137 is expressed by follicular dendritic cells and costimulates B lymphocyte activation in germinal centers. J. Leukoc. Biol. 2002, 72, 35-42.
75. Lee, U. H.; Kwack, K. B.; Park, J. W.; Kwon, B. S.; Molecular cloning of agonistic and antagonistic of biological ancibodies against human 4-1BB. Eur. J. Immunogenet. 2002, 29, 449-452.
76. Lee, U. H.; Son, J. H.; Lee, J. J.; Kwon, B.; Park, J. W.; Kwon, B. S. Humanization of antagonistic anti-human 4-1BB monoclonal antibody using a phage-displayed combinatorial library. J. Immunother. 2004, 27, 201-210.
77. Son, J. H.; Lee, U. H.; Lee, J. J.; Kwon, B.; Kwon, B. S.; Park, J. W. Humanization of agonistic anti-human 4-1BB monoclonal antibody using a phage-displayed combinatorial library. J. Immunol. Methods. 2004, 286, 187-201.
78. Xiang, J. Expression of co-stimulatory 4-1BB ligand induces significant tumor regression and protective immunity. Cancer Biother. Radiopharm. 1999, 14, 353-361.
79. Strome, S. E.; Martin, B.; Flies, D.; Tamada, K.; Chapoval, A. I.; Sargent, D. J.; Shu, S.; Chen, L. Enhanced therapeutic potential of adoptive immunotherapy by in vitro CD28/4-1BB costimulation of tumor-reactive T cells against a poorly immunogenic, major histocompatibility complex class ...-negative A9P melanoma. J. Immunother. 2000, 23, 430-437.
80. Mogi, S.; Sakurai, J.; Kohsaka, T.; Enomoto, S.; Yagita, H.; Okumura, K.; Azuma, M. Tumour rejection by gene transfer of 4-1BB ligand into a CD80(+) murine squamous cell carcinoma and the requirements of co-ctimulatory molecules on tumour and host cells. Immunology. 2000, 101, 541-547.
81. Maus, M. V.; Thomas, A. K.; Leonard, D. G.; Allman, D.; Addya, K.; Schlienger, K.; Riley, J. L.; June, C. H. Ex vivo expansion of polyclonal and antigen-specfic cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB. Nat. Biotechnol. 2002, 20, 143-148.
82. Ye, Z.; Hellstrom, I.; Hayden-ledbetter, M.; Dahlin, A.; Ledbetter, J. A.; Hellstrom, K. E. Gene therapy for cancer using-chain Fv fragments specific for 4-1BB. Nat. Med 2002, 8, 333-334.
83. Martinet, O.; Ermekova, V.; Qiao, J. Q.; Sauter, B.; Mandeli, J.; Chen, L.; Chen, S. H. Immunomodulatory gene therapy with interleukin 12 and 4-1BB ligand: long-term remission of liver metastases in a mouse model. J. Natl. Cancer Inst. 2000, 72, 931-936.
84. Chen, S. H.; Pham-Nguyen, K. B.; Martinet, O.; Huang, Y.; Yang, W.; Thung, S. N.; Chen, L.; Mittler, R.; Woo, S. L. Rejection of disseminated metastases of colon carcinoma by synergism of IL-12 gene therapy and 4-1BB costimulation. Mol. Ther. 2000, 2, 39-46.
85. Tirapu, I.; Arina, A.; Mazzolini, G.; Duarte, M.; Alfaro, C.; Feijoo, E.; Qian, C.; Chen, L.; Prieto, J.; Melero, I. Improving efficacy of interleukin-12-transfected dendritic cells injected into murine colon cancer with anti-CD137 monoclonal antibodies and alloantigens. Int. J. Cancer. 2004, 110, 51-60.
86. Ito, F.; Li, Q.; Shreiner, A. D.; Okuyama, R.; Jure-Kunkel, M. N.; Segal, T. T. and Chang. A. E. Anti-CD137 Monoclonal Antibody Administration Augments the Antitumor Efficacy of Dendritic Cell-Based Vaccines. Cancer Res. 2004, 64, 8411-8419.