Renewed interest in cancer immunotherapy with the tumor necrosis factor superfamily molecules

Cancer Immunology, Immunotherapy

Volumn 55, Issue 4, 2006, Pages 355-362

  Tamada, Koji ^a   Chen, Lieping ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD40 ANTIGEN; RECOMBINANT TUMOR NECROSIS FACTOR; RECOMBINANT TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

ANTINEOPLASTIC ACTIVITY; CANCER IMMUNOTHERAPY; DATA BASE; DRUG EFFECT; DRUG POTENCY; GENOMICS; HUMAN; MOLECULAR DYNAMICS; PRIORITY JOURNAL; REVIEW; SIDE EFFECT;

ANTIGENS, CD; ANTIGENS, CD137; ANTIGENS, CD40; ANTINEOPLASTIC AGENTS; APOPTOSIS REGULATORY PROTEINS; COMPUTATIONAL BIOLOGY; GENOMICS; HUMANS; IMMUNOTHERAPY; MEMBRANE GLYCOPROTEINS; MEMBRANE PROTEINS; NEOPLASMS; RECEPTORS, NERVE GROWTH FACTOR; RECEPTORS, TUMOR NECROSIS FACTOR; TNF-RELATED APOPTOSIS-INDUCING LIGAND; TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 14; TUMOR NECROSIS FACTOR-ALPHA;

EID: 30444442143     PISSN: 03407004     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00262-005-0081-y     Document Type: Review

References (90)

1. Afford SC, Randhawa S, Eliopoulos AG, Hubscher SG, Young LS, Adams DH (1999) CD40 activation induces apoptosis in cultured human hepatocytes via induction of cell surface Fas ligand expression and amplifies Fas-mediated hepatocyte death during allograft rejection. J Exp Med 189:441-446
2. Asher A, Mule JJ, Reichert CM, Shiloni E, Rosenberg SA (1987) Studies on the anti-tumor efficacy of systemically administered recombinant tumor necrosis factor against several murine tumors in vivo. J Immunol 138:963-974
3. Browning JL, Sizing ID, Lawton P, Bourdon PR, Rennert PD, Majeau GR, Ambrose CM, Hession C, Miatkowski K, Griffiths DA, Ngam-ek A, Meier W, Benjamin CD, Hochman PS (1997) Characterization of lymphotoxin-alpha beta complexes on the surface of mouse lymphocytes. J Immunol 159:3288-3298
4. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:3666-3670
5. Cho HR, Kwon B, Yagita H, La S, Lee EA, Kim JE, Akiba H, Kim J, Suh JH, Vinay DS, Ju SA, Kim BS, Mittler RS, Okumura K, Kwon BS (2004) Blockade of 4-1BB (CD137)/4-1BB ligand interactions increases allograft survival. Transpl Int 17:351-361
6. + T cells. J Leukoc Biol 75:785-791
7. Couderc B, Zitvogel L, Douin-Echinard V, Djennane L, Tahara H, Favre G, Lotze MT, Robbins PD (1998) Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154 (CD40 ligand) costimulatory molecules in tumor cells. Cancer Gene Ther 5:163-175
8. Creagan ET, Kovach JS, Moertel CG, Frytak S, Kvols LK (1988) A phase I clinical trial of recombinant human tumor necrosis factor. Cancer 62:2467-2471
9. Creaven PJ, Plager JE, Dupere S, Huben RP, Takita H, Mittelman A, Proefrock A (1987) Phase I clinical trial of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 20:137-144
10. Cretney E, Takeda K, Yagita H, Glaccum M, Peschon JJ, Smyth MJ (2002) Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J Immunol 168:1356-1361
11. Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG (1997) The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 7:813-820
12. Diehl L, den Boer AT, Schoenberger SP, van der Voort EI, Schumacher TN, Melief CJ, Offringa R, Toes RE (1999) CD40 activation in vivo overcomes peptide-induced peripheral cytotoxic T-lymphocyte tolerance and augments anti-tumor vaccine efficacy. Nat Med 5:774-779
13. Eggermont AM, Schraffordt Koops H, Klausner JM, Kroon BB, Schlag PM, Lienard D, van Geel AN, Hoekstra HJ, Meller I, Nieweg OE, Kettelhack C, Ben-Ari G, Pector JC, Lejeune FJ (1996) Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience. Ann Surg 224:756-764 (discussion 64-65)
14. Eliopoulos AG, Davies C, Knox PG, Gallagher NJ, Afford SC, Adams DH, Young LS (2000) CD40 induces apoptosis in carcinoma cells through activation of cytotoxic ligands of the tumor necrosis factor superfamily. Mol Cell Biol 20:5503-5515
15. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273:14363-14367
16. Fluckiger AC, Durand I, Banchereau J (1994) Interleukin 10 induces apoptotic cell death of B-chronic lymphocytic leukemia cells. J Exp Med 179:91-99
17. Funakoshi S, Longo DL, Beckwith M, Conley DK, Tsarfaty G, Tsarfaty I, Armitage RJ, Fanslow WC, Spriggs MK, Murphy WJ (1994) Inhibition of human B-cell lymphoma growth by CD40 stimulation. Blood 83:2787-2794
18. Futagawa T, Akiba H, Kodama T, Takeda K, Hosoda Y, Yagita H, Okumura K (2002) Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells. Int Immunol 14:275-286
19. Ghamande S, Hylander BL, Oflazoglu E, Lele S, Fanslow W, Repasky EA (2001) Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin. Cancer Res 61:7556-7562
20. Grell M, Zimmermann G, Gottfried E, Chen CM, Grunwald U, Huang DC, Wu Lee YH, Durkop H, Engelmann H, Scheurich P, Wajant H, Strasser A (1999) Induction of cell death by tumour necrosis factor (TNF) receptor 2, CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNF. Embo J 18:3034-3043
21. Griffith TS, Chin WA, Jackson GC, Lynch DH, Kubin MZ (1998) Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J Immunol 161:2833-2840
22. Gurunathan S, Irvine KR, Wu CY, Cohen JI, Thomas E, Prussin C, Restifo NP, Seder RA (1998) CD40 ligand/trimer DNA enhances both humoral and cellular immune responses and induces protective immunity to infectious and tumor challenge. J Immunol 161:4563-4571
23. Harrop JA, Reddy M, Dede K, Brigham-Burke M, Lyn S, Tan KB, Silverman C, Eichman C, DiPrinzio R, Spampanato J, Porter T, Holmes S, Young PR, Truneh A (1998) Antibodies to TR2 (herpes virus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines. J Immunol 161:1786-1794
24. Held J, Schulze-Osthoff K (2001) Potential and caveats of TRAIL in cancer therapy. Drug Resist Updat 4:243-252
25. Hirano A, Longo DL, Taub DD, Ferris DK, Young LS, Eliopoulos AG, Agathanggelou A, Cullen N, Macartney J, Fanslow WC, Murphy WJ (1999) Inhibition of human breast carcinoma growth by a soluble recombinant human CD40 ligand. Blood 93:2999-3007
26. Hymowitz SG, Christinger HW, Fuh G, Ultsch M, O'Connell M, Kelley RF, Ashkenazi A, de Vos AM (1999) Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Mol Cell 4:563-571
27. Ichikawa K, Liu W, Zhao L, Wang Z, Liu D, Ohtsuka T, Zhang H, Mountz JD, Koopman WJ, Kimberly RP, Zhou T (2001) Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 7:954-960
28. Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J (1997) Inhibition of death receptor signals by cellular FLIP. Nature 388:190-195
29. Ito F, Li Q, Shreiner AB, Okuyama R, Jure-Kunkel MN, Teitz-Tennenbaum S, Chang AE (2004) Anti-CD137 monoclonal antibody administration augments the antitumor efficacy of dendritic cell-based vaccines. Cancer Res 64:8411-8419
30. Jones AL, Selby P (1989) Tumour necrosis factor: clinical relevance. Cancer Surv 8:817-836
31. Kimura K, Taguchi T, Urushizaki I, Ohno R, Abe O, Furue H, Hattori T, Ichihashi H, Inoguchi K, Majima H, et al (1987) Phase I study of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 20:223-229
32. Kluin-Nelemans HC, Beverstock GC, Mollevanger P, Wessels HW, Hoogendoorn E, Willemze R, Falkenburg JH (1994) Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen. Blood 84:3134-3141
33. Lenk H, Tanneberger S, Muller U, Ebert J, Shiga T (1989) Phase II clinical trial of high-dose recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 24:391-392
34. Leverkus M, Neumann M, Mengling T, Rauch CT, Brocker EB, Krammer PH, Walczak H (2000) Regulation of tumor necrosis factor-related apoptosis-inducing ligand sensitivity in primary and transformed human keratinocytes. Cancer Res 60:553-559
35. Lienard D, Eggermont AM, Koops HS, Kroon B, Towse G, Hiemstra S, Schmitz P, Clarke J, Steinmann G, Rosenkaimer F, Lejeune FJ (1999) Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study. Melanoma Res 9:491-502
36. Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487-501
37. Manusama ER, Nooijen PT, Stavast J, de Wilt JH, Marquet RL, Eggermont AM (1998) Assessment of the role of neutrophils on the antitumor effect of TNFalpha in an in vivo isolated limb perfusion model in sarcoma-bearing brown Norway rats. J Surg Res 78:169-175
38. Mauri DN, Ebner R, Montgomery RI, Kochel KD, Cheung TC, Yu GL, Ruben S, Murphy M, Eisenberg RJ, Cohen GH, Spear PG, Ware CF (1998) LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator. Immunity 8:21-30
39. Maus MV, Thomas AK, Leonard DG, Allman D, Addya K, Schlienger K, Riley JL, June CH (2002) Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB. Nat Biotechnol 20:143-148
40. Melero I, Bach N, Hellstrom KE, Aruffo A, Mittler RS, Chen L (1998) Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB ligand: synergy with the CD28 costimulatory pathway. Eur J Immunol 28:1116-1121
41. Melero I, Johnston JV, Shufford WW, Mittler RS, Chen L (1998) NK1.1 cells express 4-1BB (CDw137) costimulatory molecule and are required for tumor immunity elicited by anti-4-1BB monoclonal antibodies. Cell Immunol 190:167-172
42. Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellstrom KE, Mittler RS, Chen L (1997) Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med 3:682-685
43. Mongkolsapaya J, Grimes JM, Chen N, Xu XN, Stuart DI, Jones EY, Screaton GR (1999) Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation. Nat Struct Biol 6:1048-1053
44. Morel Y, Truneh A, Sweet RW, Olive D, Costello RT (2001) The TNF superfamily members LIGHT and CD154 (CD40 ligand) costimulate induction of dendritic cell maturation and elicit specific CTL activity. J Immunol 167:2479-2486
45. Morris AE, Remmele RL Jr, Klinke R, Macduff BM, Fanslow WC, Armitage RJ (1999) Incorporation of an isoleucine zipper motif enhances the biological activity of soluble CD40L (CD154). J Biol Chem 274:418-423
46. Nooijen PT, Eggermont AM, Schalkwijk L, Henzen-Logmans S, de Waal RM, Ruiter DJ (1998) Complete response of melanoma-in-transit metastasis after isolated limb perfusion with tumor necrosis factor alpha and melphalan without massive tumor necrosis: a clinical and histopathological study of the delayed-type reaction pattern. Cancer Res 58:4880-4887
47. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM (1997) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277:815-818
48. Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (1997) The receptor for the cytotoxic ligand TRAIL. Science 276:111-113
49. Pardoll D (2003) Does the immune system see tumors as foreign or self? Annu Rev Immunol 21:807-839
50. Pellat-Deceunynck C, Amiot M, Robillard N, Wijdenes J, Bataille R (1996) CD11a-CD18 and CD102 interactions mediate human myeloma cell growth arrest induced by CD40 stimulation. Cancer Res 56:1909-1916
51. 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 150:771-781
52. Posner MR, Cavacini LA, Upton MP, Tillman KC, Gornstein ER, Norris CM Jr (1999) Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines. Clin Cancer Res 5:2261-2270
53. Quezada SA, Jarvinen LZ, Lind EF, Noelle RJ (2004) CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol 22:307-328
54. Renard N, Lienard D, Lespagnard L, Eggermont A, Heimann R, Lejeune F (1994) Early endothelium activation and polymorphonuclear cell invasion precede specific necrosis of human melanoma and sarcoma treated by intravascular high-dose tumour necrosis factor alpha (rTNF alpha). Int J Cancer 57:656-663
55. + T-helper and a T-killer cell. Nature 393:474-478
56. Ryo K, Kamogawa Y, Ikeda I, Yamauchi K, Yonehara S, Nagata S, Hayashi N (2000) Significance of Fas antigen-mediated apoptosis in human fulminant hepatic failure. Am J Gastroenterol 95:2047-2055
57. + T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells. Blood 88:1375-1382
58. Scheu S, Alferink J, Potzel T, Barchet W, Kalinke U, Pfeffer K (2002) Targeted disruption of LIGHT causes defects in costimulatory T cell activation and reveals cooperation with lymphotoxin beta in mesenteric lymph node genesis. J Exp Med 195:1613-1624
59. Schmaltz C, Alpdogan O, Kappel BJ, Muriglan SJ, Rotolo JA, Ongchin J, Willis LM, Greenberg AS, Eng JM, Crawford JM, Murphy GF, Yagita H, Walczak H, Peschon JJ, van den Brink MR (2002) T cells require TRAIL for optimal graft-versus-tumor activity. Nat Med 8:1433-1437
60. Schoenberger SP, Toes RE, van der Voort EI, Offringa R, Melief CJ (1998) T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393:480-483
61. Schultze JL, Cardoso AA, Freeman GJ, Seamon MJ, Daley J, Pinkus GS, Gribben JG, Nadler LM (1995) Follicular lymphomas can be induced to present alloantigen efficiently: a conceptual model to improve their tumor immunogenicity. Proc Natl Acad Sci USA 92:8200-8204
62. Schultze JL, Anderson KC, Gilleece MH, Gribben JG, Nadler LM (2001) A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2. Br J Haematol 113:455-460
63. Shaikh RB, Santee S, Granger SW, Butrovich K, Cheung T, Kronenberg M, Cheroutre H, Ware CF (2001) Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction. J Immunol 167:6330-6337
64. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818-821
65. + T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J Exp Med 186:47-55
66. + T-cell tolerance to T-cell priming through in vivo ligation of CD40. Nat Med 5:780-787
67. Takahashi C, Mittler RS, Vella AT (1999) Cutting edge: 4-1BB is a bona fide CD8 T cell survival signal. J Immunol 162:5037-5040
68. Takeda K, Hayakawa Y, Smyth MJ, Kayagaki N, Yamaguchi N, Kakuta S, Iwakura Y, Yagita H, Okumura K (2001) Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med 7:94-100
69. Takeda K, Smyth MJ, Cretney E, Hayakawa Y, Kayagaki N, Yagita H, Okumura K (2002) Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. J Exp Med 195:161-169
70. Tamada K, Shimozaki K, Chapoval AI, Zhai Y, Su J, Chen SF, Hsieh SL, Nagata S, Ni J, Chen L (2000) LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response. J Immunol 164:4105-4110
71. Tamada K, Shimozaki K, Chapoval AI, Zhu G, Sica G, Flies D, Boone T, Hsu H, Fu YX, Nagata S, Ni J, Chen L (2000) Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway. Nat Med 6:283-289
72. + T cell function in mice lacking the TNF superfamily member LIGHT. J Immunol 168:4832-4835
73. Tirapu I, Arina A, Mazzolini G, Duarte M, Alfaro C, Feijoo E, Qian C, Chen L, Prieto J, Melero I (2004) Improving efficacy of interleukin-12- transfected dendritic cells injected into murine colon cancer with anti-CD137 monoclonal antibodies and alloantigens. Int J Cancer 110:51-60
74. + T cell clones. J Immunol 144:2550-2557
75. Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5:157-163
76. Wang J, Lo JC, Foster A, Yu P, Chen HM, Wang Y, Tamada K, Chen L, Fu YX (2001) The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT. J Clin Invest 108:1771-1780
77. Watts TH (2005) TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 23:23-68
78. Weinberg AD, Rivera MM, Prell R, Morris A, Ramstad T, Vetto JT, Urba WJ, Alvord G, Bunce C, Shields J (2000) Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J Immunol 164:2160-2169
79. Wilcox RA, Chapoval AI, Gorski KS, Otsuji M, Shin T, Flies DB, Tamada K, Mittler RS, Tsuchiya H, Pardoll DM, Chen L (2002) Cutting edge: expression of functional CD137 receptor by dendritic cells. J Immunol 168:4262-4267
80. Wilcox RA, Flies DB, Wang H, Tamada K, Johnson AJ, Pease LR, Rodriguez M, Guo Y, Chen L (2002) Impaired infiltration of tumor-specific cytolytic T cells in the absence of interferon-gamma despite their normal maturation in lymphoid organs during CD137 monoclonal antibody therapy. Cancer Res 62:4413-4418
81. Wilcox RA, Flies DB, Zhu G, Johnson AJ, Tamada K, Chapoval AI, Strome SE, Pease LR, Chen L (2002) Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J Clin Invest 109:651-659
82. + cytolytic T cells and responsiveness to IL-2 but not cytolytic activity. J Immunol 169:4230-4236
83. + cytolytic T lymphocytes in vivo. Blood 103:177-184
84. Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi Y (1997) TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member pre-dominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med 186:2075-2080
85. Wuchter C, Krappmann D, Cai Z, Ruppert V, Scheidereit C, Dorken B, Ludwig WD, Karawajew L (2001) In vitro susceptibility to TRAIL-induced apoptosis of acute leukemia cells in the context of TRAIL receptor gene expression and constitutive NF-kappa B activity. Leukemia 15:921-928
86. Yamada M, Shiroko T, Kawaguchi Y, Sugiyama Y, Egilmez NK, Chen FA, Bankert RB (2001) CD40-CD40 ligand (CD154) engagement is required but not sufficient for modulating MHC class 1, ICAM-1 and Fas expression and proliferation of human non-small cell lung tumors. Int J Cancer 92:589-599
87. Ye Q, Fraser CC, Gao W, Wang L, Busfield SJ, Wang C, Qiu Y, Coyle AJ, Gutierrez-Ramos JC, Hancock WW (2002) Modulation of LIGHT-HVEM costimulation prolongs cardiac allograft survival. J Exp Med 195:795-800
88. Ye Z, Hellstrom I, Hayden-Ledbetter M, Dahlin A, Ledbetter JA, Hellstrom KE (2002) Gene therapy for cancer using single-chain Fv fragments specific for 4-1BB. Nat Med 8:343-348
89. Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS (1999) A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis. J Biol Chem 274:13733-13736
90. Yu P, Lee Y, Liu W, Chin RK, Wang J, Wang Y, Schietinger A, Philip M, Schreiber H, Fu YX (2004) Priming of naive T cells inside tumors leads to eradication of established tumors. Nat Immunol 5:141-149