Interleukin-15 in gene therapy of cancer

Current Gene Therapy

Volumn 13, Issue 1, 2013, Pages 15-30

  Ochoa, Maria C ^a   Mazzolini, Guillermo ^b   Hervas Stubbs, Sandra ^a   de Sanmamed, Miguel F ^a,c   Berraondo, Pedro ^a   Melero, Ignacio ^a,c  

^a UNIVERSITY OF NAVARRA   (Spain)

^b UNIVERSIDAD AUSTRAL   (Argentina)

^c UNIVERSITY CLINIC OF NAVARRA   (Spain)

Author keywords

Cancer; Gene therapy; Immunotherapy; Interleukin 15

Indexed keywords

CYCLOPHOSPHAMIDE; FLUOROURACIL; FOLINIC ACID; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 15 RECEPTOR ALPHA; INTERLEUKIN 2; ISOPROTEIN; JANUS KINASE 1; JANUS KINASE 3; RITUXIMAB; STAT3 PROTEIN; STAT5 PROTEIN; VIRUS VECTOR;

ARTICLE; BREAST CANCER; CANCER IMMUNOTHERAPY; CELL DEATH; CELL PROLIFERATION; COLORECTAL CANCER; CYTOKINE PRODUCTION; CYTOTOXICITY; KIDNEY CARCINOMA; KNOCKOUT MOUSE; LUNG METASTASIS; MELANOMA; NATURAL KILLER CELL; NEOPLASM; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RHESUS MONKEY; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TRANSGENIC MOUSE; TUMOR MODEL;

DENDRITIC CELLS; GENETIC THERAPY; HUMANS; INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT; INTERLEUKIN-15; INTERLEUKIN-15 RECEPTOR ALPHA SUBUNIT; INTERLEUKIN-2 RECEPTOR BETA SUBUNIT; KILLER CELLS, NATURAL; LYMPHOCYTE ACTIVATION; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84873134031     PISSN: 15665232     EISSN: 18755631     Source Type: Journal    
DOI: 10.2174/156652313804806561     Document Type: Article

References (176)

1. Grabstein KH, Eisenman J, Shanebeck K, et al. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 1994; 264: 965-8.
2. de Jong JL, Farner NL, Sondel PM. Distinctions in lymphocyte responses to IL-2 and IL-15 reflect differential ligand binding interactions with the IL-2Rbeta chain and suggest differential roles for the IL-2Ralpha and IL-15Ralpha subunits. Cytokine 1998; 10: 920-30.
3. Doherty TM, Seder RA, Sher A. Induction and regulation of IL-15 expression in murine macrophages. J Immunol 1996; 156: 735-41.
4. Onu A, Pohl T, Krause H, Bulfone-Paus S. Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms. J Immunol 1997; 158: 255-62.
5. Tagaya Y, Kurys G, Thies TA, et al. Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides. Proc Natl Acad Sci U S A 1997; 94: 14444-9.
6. Nishimura H, Yajima T, Naiki Y, et al. Differential roles of interleukin 15 mRNA isoforms generated by alternative splicing in immune responses in vivo. J Exp Med 2000; 191: 157-70.
7. Gaggero A, Azzarone B, Andrei C, et al. Differential intracellular trafficking, secretion and endosomal localization of two IL-15 isoforms. Eur J Immunol 1999; 29: 1265-74.
8. Meazza R, Gaggero A, Neglia F, et al. Expression of two interleukin-15 mRNA isoforms in human tumors does not correlate with secretion: role of different signal peptides. Eur J Immunol 1997; 27: 1049-54.
9. Bergamaschi C, Jalah R, Kulkarni V, et al. Secretion and biological activity of short signal peptide IL-15 is chaperoned by IL-15 receptor alpha in vivo. J Immunol 2009; 183: 3064-72.
10. Giri JG, Kumaki S, Ahdieh M, et al. Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor. EMBO J 1995; 14: 3654-63.
11. Carson WE, Ross ME, Baiocchi RA, et al. Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-gamma by natural killer cells in vitro. J Clin Invest 1995; 96: 2578-82.
12. Mattei F, Schiavoni G, Belardelli F, Tough DF. IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation. J Immunol 2001; 167: 1179-87.
13. Neely GG, Robbins SM, Amankwah EK, et al. Lipopolysaccharide-stimulated or granulocyte-macrophage colony-stimulating factor-stimulated monocytes rapidly express biologically active IL-15 on their cell surface independent of new protein synthesis. J Immunol 2001; 167: 5011-7.
14. Mrozek E, Anderson P, Caligiuri MA. Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells. Blood 1996; 87: 2632-40.
15. Cooper MA, Bush JE, Fehniger TA, et al. In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 2002; 100: 3633-8.
16. Carson WE, Fehniger TA, Haldar S, et al. A potential role for interleukin-15 in the regulation of human natural killer cell survival. J Clin Invest 1997; 99: 937-43.
17. Lu J, Giuntoli RL, 2nd, Omiya R, Kobayashi H, Kennedy R, Celis E. Interleukin 15 promotes antigen-independent in vitro expansion and long-term survival of antitumor cytotoxic T lymphocytes. Clin Cancer Res 2002; 8: 3877-84.
18. Elpek KG, Rubinstein MP, Bellemare-Pelletier A, Goldrath AW, Turley SJ. Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes. Proc Natl Acad Sci U S A 2010; 107: 21647-52.
19. Huntington ND, Puthalakath H, Gunn P, et al. Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1. Nat Immunol 2007; 8: 856-63.
20. Taieb J, Chaput N, Menard C, et al. A novel dendritic cell subset involved in tumor immunosurveillance. Nat Med 2006; 12: 214-9.
21. Ullrich E, Bonmort M, Mignot G, et al. Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions. J Immunol 2008; 180: 7887-97.
22. Becker TC, Wherry EJ, Boone D, et al. Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med 2002; 195: 1541-8.
23. Schluns KS, Williams K, Ma A, Zheng XX, Lefrancois L. Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells. J Immunol 2002; 168: 4827-31.
24. Zhang X, Sun S, Hwang I, Tough DF, Sprent J. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 1998; 8:591-9.
25. Edelbaum D, Mohamadzadeh M, Bergstresser PR, Sugamura K, Takashima A. Interleukin (IL)-15 promotes the growth of murine epidermal gamma delta T cells by a mechanism involving the betaand gamma c-chains of the IL-2 receptor. J Invest Dermatol 1995; 105: 837-43.
26. Dooms H, Van Belle T, Desmedt M, Rottiers P, Grooten J. Interleukin-15 redirects the outcome of a tolerizing T-cell stimulus from apoptosis to anergy. Blood 2000; 96: 1006-12.
27. Armitage RJ, Macduff BM, Eisenman J, Paxton R, Grabstein KH. IL-15 has stimulatory activity for the induction of B cell proliferation and differentiation. J Immunol 1995; 154: 483-90.
28. Oelert T, Papatriantafyllou M, Pougialis G, Hammerling GJ, Arnold B, Schuler T. Irradiation and IL-15 promote loss of CD8 Tcell tolerance in response to lymphopenia. Blood; 115: 2196-202.
29. Stoklasek TA, Colpitts SL, Smilowitz HM, Lefrancois L. MHC class I and TCR avidity control the CD8 T cell response to IL-15/IL-15Ralpha complex. J Immunol 2010; 185: 6857-65.
30. Epron G, Ame-Thomas P, Le Priol J, et al. Monocytes and T cells cooperate to favor normal and follicular lymphoma B-cell growth: role of IL-15 and CD40L signaling. Leukemia 2012; 26: 139-48.
31. McInnes IB, Leung BP, Sturrock RD, Field M, Liew FY. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. Nat Med 1997; 3: 189-95.
32. Mori A, Suko M, Kaminuma O, et al. IL-15 promotes cytokine production of human T helper cells. J Immunol 1996; 156: 2400-5.
33. Musso T, Calosso L, Zucca M, et al. Interleukin-15 activates proinflammatory and antimicrobial functions in polymorphonuclear cells. Infect Immun 1998; 66: 2640-7.
34. Girard D, Paquet ME, Paquin R, Beaulieu AD. Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and apoptosis by IL-15. Blood 1996; 88: 3176-84.
35. Angiolillo AL, Kanegane H, Sgadari C, Reaman GH, Tosato G. Interleukin-15 promotes angiogenesis in vivo. Biochem Biophys Res Commun 1997; 233: 231-7.
36. Wilkinson PC, Liew FY. Chemoattraction of human blood T lymphocytes by interleukin-15. J Exp Med 1995; 181: 1255-9.
37. Nieto M, del Pozo MA, Sanchez-Madrid F. Interleukin-15 induces adhesion receptor redistribution in T lymphocytes. Eur J Immunol 1996; 26: 1302-7.
38. Johnston JA, Bacon CM, Finbloom DS, et al. Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15. Proc Natl Acad Sci U S A 1995; 92: 8705-9.
39. Marzec M, Liu X, Kasprzycka M, et al. IL-2-and IL-15-induced activation of the rapamycin-sensitive mTORC1 pathway in malignant CD4+ T lymphocytes. Blood 2008; 111: 2181-9.
40. de Totero D, Meazza R, Capaia M, et al. The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways. Blood 2008; 111: 517-24.
41. Adunyah SE, Wheeler BJ, Cooper RS. Evidence for the involvement of LCK and MAP kinase (ERK-1) in the signal transduction mechanism of interleukin-15. Biochem Biophys Res Commun 1997; 232: 754-8.
42. Neely GG, Epelman S, Ma LL, et al. Monocyte surface-bound IL-15 can function as an activating receptor and participate in reverse signaling. J Immunol 2004; 172: 4225-34.
43. Lugli E, Goldman CK, Perera LP, et al. Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates. Blood 2010; 116: 3238-48.
44. Sneller MC, Kopp WC, Engelke KJ, et al. IL-15 administered by continuous infusion to rhesus macaques induces massive expansion of CD8+ T effector memory population in peripheral blood. Blood 2011; 118: 6845-8.
45. Ohteki T, Ho S, Suzuki H, Mak TW, Ohashi PS. Role for IL-15/IL-15 receptor beta-chain in natural killer 1.1+ T cell receptor-alpha beta+ cell development. J Immunol 1997; 159: 5931-5.
46. Lorenzen I, Dingley AJ, Jacques Y, Grotzinger J. The structure of the interleukin-15 alpha receptor and its implications for ligand binding. J Biol Chem 2006; 281: 6642-7.
47. Anderson DM, Kumaki S, Ahdieh M, et al. Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes. J Biol Chem 1995; 270: 29862-9.
48. Chae DW, Nosaka Y, Strom TB, Maslinski W. Distribution of IL-15 receptor alpha-chains on human peripheral blood mononuclear cells and effect of immunosuppressive drugs on receptor expression. J Immunol 1996; 157: 2813-9.
49. Wei X, Orchardson M, Gracie JA, et al. The Sushi domain of soluble IL-15 receptor alpha is essential for binding IL-15 and inhibiting inflammatory and allogenic responses in vitro and in vivo. J Immunol 2001; 167: 277-82.
50. Wu Z, Xue HH, Bernard J, et al. The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15Ralpha function but is not required for trans-presentation. Blood 2008; 112: 4411-9.
51. Dubois S, Mariner J, Waldmann TA, Tagaya Y. IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells. Immunity 2002; 17: 537-47.
52. Giron-Michel J, Giuliani M, Fogli M, et al. Membrane-bound and soluble IL-15/IL-15Ralpha complexes display differential signaling and functions on human hematopoietic progenitors. Blood 2005; 106: 2302-10.
53. Mortier E, Woo T, Advincula R, Gozalo S, Ma A. IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med 2008; 205: 1213-25.
54. Muller JR, Waldmann TA, Kruhlak MJ, Dubois S. Paracrine and transpresentation functions of IL-15 are mediated by diverse splice versions of IL-15Ralpha in human monocytes and dendritic cells. J Biol Chem 2012; 287(48): 40328-38.
55. Olsen SK, Ota N, Kishishita S, et al. Crystal Structure of the interleukin-15. interleukin-15 receptor alpha complex: insights into trans and cis presentation. J Biol Chem 2007; 282: 37191-204.
56. Chirifu M, Hayashi C, Nakamura T, et al. Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans. Nat Immunol 2007; 8: 1001-7.
57. Meazza R, Basso S, Gaggero A, et al. Interleukin (IL)-15 induces survival and proliferation of the growth factor-dependent acute myeloid leukemia M-07e through the IL-2 receptor beta/gamma. Int J Cancer 1998; 78: 189-95.
58. Sandau MM, Schluns KS, Lefrancois L, Jameson SC. Cutting edge: transpresentation of IL-15 by bone marrow-derived cells necessitates expression of IL-15 and IL-15R alpha by the same cells. J Immunol 2004; 173: 6537-41.
59. Burkett PR, Koka R, Chien M, Chai S, Boone DL, Ma A. Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis. J Exp Med 2004; 200: 825-34.
60. Stonier SW, Ma LJ, Castillo EF, Schluns KS. Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation. Blood 2008; 112: 4546-54.
61. Castillo EF, Stonier SW, Frasca L, Schluns KS. Dendritic cells support the in vivo development and maintenance of NK cells via IL-15 trans-presentation. J Immunol 2009; 183: 4948-56.
62. Boudreau JE, Stephenson KB, Wang F, et al. IL-15 and type I interferon are required for activation of tumoricidal NK cells by virus-infected dendritic cells. Cancer Res 2011; 71: 2497-2506.
63. Vujanovic L, Szymkowski DE, Alber S, Watkins SC, Vujanovic NL, Butterfield LH. Virally infected and matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15. Blood 2010; 116: 575-83.
64. Lee GA, Liou YH, Wang SW, Ko KL, Jiang ST, Liao NS. Different NK cell developmental events require different levels of IL-15 trans-presentation. J Immunol 2011; 187: 1212-21.
65. Lodolce JP, Burkett PR, Boone DL, Chien M, Ma A. T cellindependent interleukin 15Ralpha signals are required for bystander proliferation. J Exp Med 2001; 194: 1187-94.
66. Koka R, Burkett PR, Chien M, et al. Interleukin (IL)-15R[alpha]-deficient natural killer cells survive in normal but not IL-15R[alpha]-deficient mice. J Exp Med 2003; 197: 977-84.
67. Wittnebel S, Da Rocha S, Giron-Michel J, et al. Membrane-bound interleukin (IL)-15 on renal tumor cells rescues natural killer cells from IL-2 starvation-induced apoptosis. Cancer Res 2007; 67: 5594-9.
68. Khawam K, Giron-Michel J, Gu Y, et al. Human renal cancer cells express a novel membrane-bound interleukin-15 that induces, in response to the soluble interleukin-15 receptor alpha chain, epithelial-to-mesenchymal transition. Cancer Res 2009; 69: 1561-9.
69. Giuliani M, Giron-Michel J, Negrini S, et al. Generation of a novel regulatory NK cell subset from peripheral blood CD34+ progenitors promoted by membrane-bound IL-15. PLoS One 2008; 3: e2241.
70. Mortier E, Bernard J, Plet A, Jacques Y. Natural, proteolytic release of a soluble form of human IL-15 receptor alpha-chain that behaves as a specific, high affinity IL-15 antagonist. J Immunol 2004; 173: 1681-8.
71. Badoual C, Bouchaud G, Agueznay Nel H, et al. The soluble alpha chain of interleukin-15 receptor: a proinflammatory molecule associated with tumor progression in head and neck cancer. Cancer Res 2008; 68: 3907-14.
72. Bouchaud G, Garrigue-Antar L, Sole V, et al. The exon-3-encoded domain of IL-15ralpha contributes to IL-15 high-affinity binding and is crucial for the IL-15 antagonistic effect of soluble IL-15Ralpha. J Mol Biol 2008; 382: 1-12.
73. Mortier E, Quemener A, Vusio P, et al. Soluble interleukin-15 receptor alpha (IL-15R alpha)-sushi as a selective and potent agonist of IL-15 action through IL-15R beta/gamma. Hyperagonist IL-15 x IL-15R alpha fusion proteins. J Biol Chem 2006; 281: 1612-9.
74. Meissner U, Blum H, Schnare M, Rollinghoff M, Gessner A. A soluble form of the murine common gamma chain is present at high concentrations in vivo and suppresses cytokine signaling. Blood 2001; 97: 183-91.
75. Dummer R, Posseckert G, Sugamura K, Grundmann H, Burg G. Circulating interleukin-2 receptors are a group of multimeric proteins with immunoreactivity for interleukin-2 receptor alpha, beta, and gamma chains. J Interferon Cytokine Res 1996; 16: 315-20.
76. Waldmann T, Tagaya Y, Bamford R. Interleukin-2, interleukin-15, and their receptors. Int Rev Immunol 1998; 16: 205-26.
77. Tagaya Y, Bamford RN, DeFilippis AP, Waldmann TA. IL-15: a pleiotropic cytokine with diverse receptor/signaling pathways whose expression is controlled at multiple levels. Immunity 1996; 4: 329-36.
78. Kennedy MK, Glaccum M, Brown SN, et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 2000; 191: 771-80.
79. Lodolce JP, Boone DL, Chai S, et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 1998; 9: 669-76.
80. Yoshizawa K, Nakajima S, Notake T, Miyagawa S, Hida S, Taki S. IL-15-high-responder developing NK cells bearing Ly49 receptors in IL-15-/-mice. J Immunol; 187: 5162-9.
81. Chaudhry UI, Plitas G, Burt BM, Kingham TP, Raab JR, DeMatteo RP. NK dendritic cells expanded in IL-15 exhibit antitumor responses in vivo. J Immunol 2007; 179: 4654-60.
82. Ohteki T, Maki C, Koyasu S. Overexpression of Bcl-2 differentially restores development of thymus-derived CD4-8+ T cells and intestinal intraepithelial T cells in IFN-regulatory factor-1-deficient mice. J Immunol 2001; 166: 6509-13.
83. Yajima T, Nishimura H, Wajjwalku W, Harada M, Kuwano H, Yoshikai Y. Overexpression of interleukin-15 in vivo enhances antitumor activity against MHC class I-negative and-positive malignant melanoma through augmented NK activity and cytotoxic Tcell response. Int J Cancer 2002; 99: 573-8.
84. Fehniger TA, Suzuki K, Ponnappan A, et al. Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells. J Exp Med 2001; 193: 219-31.
85. Yokohama A, Mishra A, Mitsui T, et al. A novel mouse model for the aggressive variant of NK cell and T cell large granular lymphocyte leukemia. Leuk Res 2010; 34: 203-9.
86. Yu J, Mitsui T, Wei M, et al. NKp46 identifies an NKT cell subset susceptible to leukemic transformation in mouse and human. J Clin Invest 2011; 121: 1456-70.
87. Marks-Konczalik J, Dubois S, Losi JM, et al. IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc Natl Acad Sci U S A 2000; 97: 11445-50.
88. Sato N, Sabzevari H, Fu S, et al. Development of an IL-15-autocrine CD8 T-cell leukemia in IL-15-transgenic mice requires the cis expression of IL-15Ralpha. Blood; 117: 4032-40.
89. Evans R, Fuller JA, Christianson G, Krupke DM, Troutt AB. IL-15 mediates anti-tumor effects after cyclophosphamide injection of tumor-bearing mice and enhances adoptive immunotherapy: the potential role of NK cell subpopulations. Cell Immunol 1997; 179: 66-73.
90. Cao S, Troutt AB, Rustum YM. Interleukin 15 protects against toxicity and potentiates antitumor activity of 5-fluorouracil alone and in combination with leucovorin in rats bearing colorectal cancer. Cancer Res 1998; 58: 1695-9.
91. Jakobisiak M, Golab J, Lasek W. Interleukin 15 as a promising candidate for tumor immunotherapy. Cytokine Growth Factor Rev 2011; 22: 99-108.
92. Tang F, Zhao LT, Jiang Y, Ba de N, Cui LX, He W. Activity of recombinant human interleukin-15 against tumor recurrence and metastasis in mice. Cell Mol Immunol 2008; 5: 189-96.
93. Le Maux Chansac B, Misse D, Richon C, et al. Potentiation of NK cell-mediated cytotoxicity in human lung adenocarcinoma: role of NKG2D-dependent pathway. Int Immunol 2008; 20: 801-10.
94. Sutherland CL, Rabinovich B, Chalupny NJ, Brawand P, Miller R, Cosman D. ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15. Blood 2006; 108: 1313-9.
95. Moga E, Alvarez E, Canto E, et al. NK cells stimulated with IL-15 or CpG ODN enhance rituximab-dependent cellular cytotoxicity against B-cell lymphoma. Exp Hematol 2008; 36: 69-77.
96. Wang X, Berger C, Wong CW, Forman SJ, Riddell SR, Jensen MC. Engraftment of human central memory-derived effector CD8+ T cells in immunodeficient mice. Blood; 117: 1888-98.
97. King JW, Thomas S, Corsi F, et al. IL15 can reverse the unresponsiveness of Wilms' tumor antigen-specific CTL in patients with prostate cancer. Clin Cancer Res 2009; 15: 1145-54.
98. Rubinstein MP, Kadima AN, Salem ML, Nguyen CL, Gillanders WE, Cole DJ. Systemic administration of IL-15 augments the antigen-specific primary CD8+ T cell response following vaccination with peptide-pulsed dendritic cells. J Immunol 2002; 169: 4928-35.
99. Pettit DK, Bonnert TP, Eisenman J, et al. Structure-function studies of interleukin 15 using site-specific mutagenesis, polyethylene glycol conjugation, and homology modeling. J Biol Chem 1997; 272: 2312-8.
100. Kukita T, Arima N, Matsushita K, et al. Autocrine and/or paracrine growth of adult T-cell leukaemia tumour cells by interleukin 15. Br J Haematol 2002; 119: 467-74.
101. Asadullah K, Haeussler-Quade A, Gellrich S, et al. IL-15 and IL-16 overexpression in cutaneous T-cell lymphomas: stage-dependent increase in mycosis fungoides progression. Exp Dermatol 2000; 9: 248-51.
102. Qin JZ, Zhang CL, Kamarashev J, Dummer R, Burg G, Dobbeling U. Interleukin-7 and interleukin-15 regulate the expression of the bcl-2 and c-myb genes in cutaneous T-cell lymphoma cells. Blood 2001; 98: 2778-83.
103. Tinhofer I, Marschitz I, Henn T, Egle A, Greil R. Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma. Blood 2000; 95: 610-8.
104. Kuniyasu H, Ohmori H, Sasaki T, et al. Production of interleukin 15 by human colon cancer cells is associated with induction of mucosal hyperplasia, angiogenesis, and metastasis. Clin Cancer Res 2003; 9: 4802-10.
105. Dubois S, Patel HJ, Zhang M, Waldmann TA, Muller JR. Preassociation of IL-15 with IL-15R alpha-IgG1-Fc enhances its activity on proliferation of NK and CD8+/CD44high T cells and its antitumor action. J Immunol 2008; 180: 2099-106.
106. Rubinstein MP, Kovar M, Purton JF, et al. Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha}. Proc Natl Acad Sci U S A 2006; 103: 9166-71.
107. Wu Z, Xu Y. IL-15R alpha-IgG1-Fc enhances IL-2 and IL-15 antitumor action through NK and CD8+ T cells proliferation and activation. J Mol Cell Biol 2010; 2: 217-22.
108. Stoklasek TA, Schluns KS, Lefrancois L. Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol 2006; 177: 6072-80.
109. Epardaud M, Elpek KG, Rubinstein MP, et al. Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. Cancer Res 2008; 68: 2972-83.
110. Bessard A, Sole V, Bouchaud G, Quemener A, Jacques Y. High antitumor activity of RLI, an interleukin-15 (IL-15)-IL-15 receptor alpha fusion protein, in metastatic melanoma and colorectal cancer. Mol Cancer Ther 2009; 8: 2736-45.
111. Stephan MT, Moon JJ, Um SH, Bershteyn A, Irvine DJ. Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat Med 2010; 16: 1035-41.
112. Kaspar M, Trachsel E, Neri D. The antibody-mediated targeted delivery of interleukin-15 and GM-CSF to the tumor neovasculature inhibits tumor growth and metastasis. Cancer Res 2007; 67: 4940-8.
113. Kermer V, Baum V, Hornig N, Kontermann RE, Muller D. An antibody fusion protein for cancer immunotherapy mimicking IL-15 trans-presentation at the tumor site. Mol Cancer Ther 2012; 11(6): 1279-88.
114. Meazza R, Lollini PL, Nanni P, et al. Gene transfer of a secretable form of IL-15 in murine adenocarcinoma cells: effects on tumorigenicity, metastatic potential and immune response. Int J Cancer 2000; 87: 574-81.
115. Comes A, Di Carlo E, Musiani P, et al. IFN-gamma-independent synergistic effects of IL-12 and IL-15 induce anti-tumor immune responses in syngeneic mice. Eur J Immunol 2002; 32: 1914-23.
116. Hazama S, Noma T, Wang F, et al. Tumour cells engineered to secrete interleukin-15 augment anti-tumour immune responses in vivo. Br J Cancer 1999; 80: 1420-6.
117. Croce M, Meazza R, Orengo AM, et al. Sequential immunogene therapy with interleukin-12-and interleukin-15-engineered neuroblastoma cells cures metastatic disease in syngeneic mice. Clin Cancer Res 2005; 11: 735-42.
118. Yoshimuta T. Gene therapy for murine lung cancer using an adenoviral vector expressing interleukin-15. Kurume Med J 2004; 51: 225-33.
119. Di Carlo E, Meazza R, Basso S, et al. Dissimilar anti-tumour reactions induced by tumour cells engineered with the interleukin-2 or interleukin-15 gene in nude mice. J Pathol 2000; 191: 193-201.
120. Yoshida Y, Tasaki K, Miyauchi M, et al. Impaired tumorigenicity of human pancreatic cancer cells retrovirally transduced with interleukin-12 or interleukin-15 gene. Cancer Gene Ther 2000; 7: 324-31.
121. Di Carlo E, Comes A, Basso S, et al. The combined action of IL-15 and IL-12 gene transfer can induce tumor cell rejection without T and NK cell involvement. J Immunol 2000; 165: 3111-8.
122. Orengo AM, Di Carlo E, Comes A, et al. Tumor cells engineered with IL-12 and IL-15 genes induce protective antibody responses in nude mice. J Immunol 2003; 171: 569-75.
123. Vera M, Razquin N, Prieto J, Melero I, Fortes P, Gonzalez-Aseguinolaza G. Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells. Mol Ther 2005; 12: 950-9.
124. Suzuki K, Nakazato H, Matsui H, et al. NK cell-mediated antitumor immune response to human prostate cancer cell, PC-3: immunogene therapy using a highly secretable form of interleukin-15 gene transfer. J Leukoc Biol 2001; 69: 531-7.
125. Kimura K, Nishimura H, Hirose K, Matsuguchi T, Nimura Y, Yoshikai Y. Immunogene therapy of murine fibrosarcoma using IL-15 gene with high translation efficiency. Eur J Immunol 1999; 29: 1532-42.
126. Rowley J, Monie A, Hung CF, Wu TC. Inhibition of tumor growth by NK1.1+ cells and CD8+ T cells activated by IL-15 through receptor beta/common gamma signaling in trans. J Immunol 2008; 181: 8237-47.
127. Kobayashi H, Dubois S, Sato N, et al. Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 2005; 105: 721-7.
128. Liu RB, Engels B, Arina A, et al. Densely granulated murine NK cells eradicate large solid tumors. Cancer Res 2012; 72: 1964-74.
129. Tasaki K, Yoshida Y, Miyauchi M, et al. Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effects in immunocompetent and immunocompromised hosts. Cancer Gene Ther 2000; 7: 255-61.
130. Wysocka M, Benoit BM, Newton S, Azzoni L, Montaner LJ, Rook AH. Enhancement of the host immune responses in cutaneous Tcell lymphoma by CpG oligodeoxynucleotides and IL-15. Blood 2004; 104: 4142-9.
131. Dubsky P, Saito H, Leogier M, et al. IL-15-induced human DC efficiently prime melanoma-specific naive CD8+ T cells to differentiate into CTL. Eur J Immunol 2007; 37: 1678-90.
132. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012; 12: 265-77.
133. Kutzler MA, Robinson TM, Chattergoon MA, et al. Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol 2005; 175: 112-23.
134. Gatza E, Okada CY. Adjuvant IL-15 does not enhance the efficacy of tumor cell lysate-pulsed dendritic cell vaccines for active immunotherapy of T cell lymphoma. Cancer Immunol Immunother 2006; 55: 420-32.
135. Humbert JM, Halary F. Viral and non-viral methods to genetically modify dendritic cells. Curr Gene Ther 2012; 12: 127-36.
136. Tian S, Liu Z, Donahue C, Noh HS, Falo LD, Jr., You Z. Transcriptional IL-15-directed in vivo DC targeting DNA vaccine. Gene Ther 2009; 16: 1260-70.
137. Steel JC, Ramlogan CA, Yu P, et al. Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help. Cancer Res 2010; 70: 1072-81.
138. Chang SY, Lee KC, Ko SY, Ko HJ, Kang CY. Enhanced efficacy of DNA vaccination against Her-2/neu tumor antigen by genetic adjuvants. Int J Cancer 2004; 111: 86-95.
139. Kowalczyk A, Wierzbicki A, Gil M, et al. Induction of protective immune responses against NXS2 neuroblastoma challenge in mice by immunotherapy with GD2 mimotope vaccine and IL-15 and IL-21 gene delivery. Cancer Immunol Immunother 2007; 56: 1443-58.
140. Kishida T, Asada H, Itokawa Y, et al. Interleukin (IL)-21 and IL-15 genetic transfer synergistically augments therapeutic antitumor immunity and promotes regression of metastatic lymphoma. Mol Ther 2003; 8: 552-8.
141. Nathwani AC, Tuddenham EG, Rangarajan S, et al. Adenovirusassociated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 2011; 365: 2357-65.
142. Yu YL, Wei CW, Chen YL, Chen MH, Yiang GT. Immunotherapy of breast cancer by single delivery with rAAV2-mediated interleukin-15 expression. Int J Oncol 2010; 36: 365-70.
143. Yiang GT, Harn HJ, Yu YL, et al. Immunotherapy: rAAV2 expressing interleukin-15 inhibits HeLa cell tumor growth in mice. J Biomed Sci 2009; 16: 47.
144. Marshall JL, Gulley JL, Arlen PM, et al. Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas. J Clin Oncol 2005; 23: 720-31.
145. Kudo-Saito C, Wansley EK, Gruys ME, Wiltrout R, Schlom J, Hodge JW. Combination therapy of an orthotopic renal cell carcinoma model using intratumoral vector-mediated costimulation and systemic interleukin-2. Clin Cancer Res 2007; 13: 1936-46.
146. Tseng JC, Hurtado A, Yee H, et al. Using sindbis viral vectors for specific detection and suppression of advanced ovarian cancer in animal models. Cancer Res 2004; 64: 6684-92.
147. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-917.
148. Chang CM, Lo CH, Shih YM, et al. Treatment of hepatocellular carcinoma with adeno-associated virus encoding interleukin-15 superagonist. Hum Gene Ther 2010; 21: 611-21.
149. Zhou X, Li X, Gou M, et al. Antitumoral efficacy by systemic delivery of heparin conjugated polyethylenimine-plasmid interleukin-15 complexes in murine models of lung metastasis. Cancer Sci 2011; 102: 1403-9.
150. Yang Z, Wang L, Wang H, et al. A novel mimovirus vaccine containing survivin epitope with adjuvant IL-15 induces long-lasting cellular immunity and high antitumor efficiency. Mol Immunol 2008; 45: 1674-81.
151. Matsumoto K, Kikuchi E, Horinaga M, et al. Intravesical interleukin-15 gene therapy in an orthotopic bladder cancer model. Hum Gene Ther 2011; 22: 1423-32.
152. Ugen KE, Kutzler MA, Marrero B, et al. Regression of subcutaneous B16 melanoma tumors after intratumoral delivery of an IL-15-expressing plasmid followed by in vivo electroporation. Cancer Gene Ther 2006; 13: 969-74.
153. Lucas ML, Heller L, Coppola D, Heller R. IL-12 plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16. F10 melanoma. Mol Ther 2002; 5: 668-75.
154. Melcher A, Parato K, Rooney CM, Bell JC. Thunder and lightning: immunotherapy and oncolytic viruses collide. Mol Ther 2011; 19: 1008-16.
155. Jiang H, Gomez-Manzano C, Lang FF, Alemany R, Fueyo J. Oncolytic adenovirus: preclinical and clinical studies in patients with human malignant gliomas. Curr Gene Ther 2009; 9: 422-27.
156. Giedlin MA, Cook DN, Dubensky TW, Jr. Vesicular stomatitis virus: an exciting new therapeutic oncolytic virus candidate for cancer or just another chapter from Field's Virology? Cancer Cell 2003; 4: 241-3.
157. Stephenson KB, Barra NG, Davies E, Ashkar AA, Lichty BD. Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity. Cancer Gene Ther 2012; 19: 238-46.
158. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med 2004; 10: 909-15.
159. Morgan RA, Dudley ME, Wunderlich JR, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126-9.
160. Hoyos V, Savoldo B, Quintarelli C, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 2010; 24: 1160-70.
161. Quintarelli C, Vera JF, Savoldo B, et al. Co-expression of cytokine and suicide genes to enhance the activity and safety of tumorspecific cytotoxic T lymphocytes. Blood 2007; 110: 2793-802.
162. Markley JC, Sadelain M. IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice. Blood 2010; 115: 3508-19.
163. Ozdemir O, Ravindranath Y, Savasan S. Mechanisms of superior anti-tumor cytotoxic response of interleukin 15-induced lymphokine-activated killer cells. J Immunother 2005; 28: 44-52.
164. Weiss JM, Back TC, Scarzello AJ, et al. Successful immunotherapy with IL-2/anti-CD40 induces the chemokine-mediated mitigation of an immunosuppressive tumor microenvironment. Proc Natl Acad Sci U S A 2009; 106: 19455-60.
165. Lasek W, Basak G, Switaj T, et al. Complete tumour regressions induced by vaccination with IL-12 gene-transduced tumour cells in combination with IL-15 in a melanoma model in mice. Cancer Immunol Immunother 2004; 53: 363-72.
166. Basak GW, Zapala L, Wysocki PJ, Mackiewicz A, Jakobisiak M, Lasek W. Interleukin 15 augments antitumor activity of cytokine gene-modified melanoma cell vaccines in a murine model. Oncol Rep 2008; 19: 1173-9.
167. Yu P, Steel JC, Zhang M, Morris JC, Waldmann TA. Simultaneous blockade of multiple immune system inhibitory checkpoints enhances antitumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model. Clin Cancer Res 2010; 16: 6019-28.
168. Moga E, Canto E, Vidal S, Juarez C, Sierra J, Briones J. Interleukin-15 enhances rituximab-dependent cytotoxicity against chronic lymphocytic leukemia cells and overcomes transforming growth factor beta-mediated immunosuppression. Exp Hematol 2011; 39: 1064-71.
169. Zhang M, Yao Z, Dubois S, Ju W, Muller JR, Waldmann TA. Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer. Proc Natl Acad Sci U S A 2009; 106: 7513-8.
170. Chapoval AI, Fuller JA, Kremlev SG, Kamdar SJ, Evans R. Combination chemotherapy and IL-15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cellmediated effects antagonized by B cells. J Immunol 1998; 161: 6977-84.
171. Roychowdhury S, May KF, Jr., Tzou KS, et al. Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose interleukin 15 but not low-dose interleukin 2. Cancer Res 2004; 64: 8062-7.
172. Kimura K, Nishimura H, Matsuzaki T, Yokokura T, Nimura Y, Yoshikai Y. Synergistic effect of interleukin-15 and interleukin-12 on antitumor activity in a murine malignant pleurisy model. Cancer Immunol Immunother 2000; 49: 71-7.
173. Habibi M, Kmieciak M, Graham L, Morales JK, Bear HD, Manjili MH. Radiofrequency thermal ablation of breast tumors combined with intralesional administration of IL-7 and IL-15 augments antitumor immune responses and inhibits tumor development and metastasis. Breast Cancer Res Treat 2009; 114: 423-31.
174. Lin CY, Chuang TF, Liao KW, Huang YJ, Pai CC, Chu RM. Combined immunogene therapy of IL-6 and IL-15 enhances anti-tumor activity through augmented NK cytotoxicity. Cancer Lett 2008; 272: 285-95.
175. Chou PC, Chuang TF, Jan TR, et al. Effects of immunotherapy of IL-6 and IL-15 plasmids on transmissible venereal tumor in beagles. Vet Immunol Immunopathol 2009; 130: 25-34.
176. Kaur B, Cripe TP, Chiocca EA. "Buy one get one free": armed viruses for the treatment of cancer cells and their microenvironment. Curr Gene Ther 2009; 9: 341-55.