Characterization and favorable in vivo properties of heterodimeric soluble IL-15•IL-15Rα cytokine compared to IL-15 monomer

Journal of Biological Chemistry

Volumn 288, Issue 25, 2013, Pages 18093-18103

  Chertova, Elena ^a   Bergamaschi, Cristina ^b   Chertov, Oleg ^c   Sowder, Raymond ^a   Bear, Jenifer ^d   Roser, James D ^a   Beach, Rachel K ^b,d   Lifson, Jeffrey D ^a   Felber, Barbara K ^d   Pavlakis, George N ^b  

^a AIDS and Cancer Virus Program   (United States)

^b SAIC FREDERICK INC   (United States)

^c Center for Cancer Research   (United States)

^d NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLINICAL APPLICATION; CYTOKINES; GLYCOSYLATED; HETERO DIMERS; HUMAN CELLS; IN-VIVO;

BIOCHEMISTRY; BIOLOGY;

BIOMOLECULES;

HETERODIMER; INTERLEUKIN 15; INTERLEUKIN 15 INTERLEUKIN 15 RECEPTOR ALPHA HETERODIMER; MONOMER; UNCLASSIFIED DRUG;

ADOPTIVE TRANSFER; AMINO ACID SEQUENCE; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL EXPANSION; CELL STRAIN HEK293; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DRUG HALF LIFE; FEMALE; GENE TRANSFER; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; MAXIMUM PLASMA CONCENTRATION; MOUSE; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN GLYCOSYLATION; PROTEIN PROCESSING; PROTEIN PURIFICATION; SPLEEN CELL; T LYMPHOCYTE;

CD8+ T CELLS; GLYCOSYLATION; HEK293 HUMAN CELL; HETERODIMERIC CYTOKINE; HPLC; INTERLEUKIN; INTERLEUKIN-15; NATURAL KILLER (NK) CELL; PROTEOLYTIC CLEAVAGE; T CELL;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CELL PROLIFERATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FEMALE; GLYCOSYLATION; HEK293 CELLS; HUMANS; IMMUNOBLOTTING; INTERLEUKIN-15; INTERLEUKIN-15 RECEPTOR ALPHA SUBUNIT; KILLER CELLS, NATURAL; MICE; MICE, INBRED C57BL; MOLECULAR SEQUENCE DATA; MULTIPROTEIN COMPLEXES; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEOLYSIS; SOLUBILITY; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION; T-LYMPHOCYTES;

EID: 84880078963     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.461756     Document Type: Article

References (60)

1. Berard, M., Brandt, K., Bulfone-Paus, S., and Tough, D. F. (2003) IL-15 promotes the survival of naive and memory phenotype CD8+ T cells. J. Immunol. 170, 5018-5026 (Pubitemid 36554732)
2. Carson, W. E., Giri, J. G., Lindemann, M. J., Linett, M. L., Ahdieh, M., Paxton, R., Anderson, D., Eisenmann, J., Grabstein, K., and Caligiuri, M. A. (1994) Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J. Exp. Med. 180, 1395-1403 (Pubitemid 24289613)
3. Ma, A., Koka, R., and Burkett, P. (2006) Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu. Rev. Immunol. 24, 657-679
4. Tan, J. T., Ernst, B., Kieper, W. C., LeRoy, E., Sprent, J., and Surh, C. D. (2002) Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J. Exp. Med. 195, 1523-1532 (Pubitemid 34666066)
5. Zhang, X., Sun, S., Hwang, I., Tough, D. F., and Sprent, J. (1998) Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8, 591-599 (Pubitemid 28264750)
6. Dubois, S., Patel, H. J., Zhang, M., Waldmann, T. A., and Müller, J. R. (2008) Preassociation of IL-15 with IL-15R α-IgG1-Fc enhances its activity on proliferation of NK and CD8+/CD44 high T cells and its antitumor action. J. Immunol. 180, 2099-2106
7. Epardaud, M., Elpek, K. G., Rubinstein, M. P., Yonekura, A. R., Bellemare-Pelletier, A., Bronson, R., Hamerman, J. A., Goldrath, A. W., and Turley, S. J. (2008) Interleukin-15/interleukin-15Rα complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. Cancer Res. 68, 2972-2983 (Pubitemid 351556298)
8. Klebanoff, C. A., Finkelstein, S. E., Surman, D. R., Lichtman, M. K., Gattinoni, L., Theoret, M. R., Grewal, N., Spiess, P. J., Antony, P. A., Palmer, D. C., Tagaya, Y., Rosenberg, S. A., Waldmann, T. A., and Restifo, N. P. (2004) IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc. Natl. Acad. Sci. U.S.A. 101, 1969-1974 (Pubitemid 38228999)
9. Kobayashi, H., Dubois, S., Sato, N., Sabzevari, H., Sakai, Y., Waldmann, T. A., and Tagaya, Y. (2005) Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 105, 721-727 (Pubitemid 40070758)
10. Stoklasek, T. A., Schluns, K. S., and Lefrançois, L. (2006) Combined IL-15/ IL-15Rα immunotherapy maximizes IL-15 activity in vivo. J. Immunol. 177, 6072-6080 (Pubitemid 44628822)
11. Teague, R. M., Sather, B. D., Sacks, J. A., Huang, M. Z., Dossett, M. L., Morimoto, J., Tan, X., Sutton, S. E., Cooke, M. P., Ohlén, C., and Greenberg, P. D. (2006) Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors. Nat. Med. 12, 335-341 (Pubitemid 43355083)
12. Zhang, M., Yao, Z., Dubois, S., Ju, W., Müller, J. R., and Waldmann, T. A. (2009) 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. 106, 7513-7518
13. Cheever, M. A. (2008) Twelve immunotherapy drugs that could cure cancers. Immunol. Rev. 222, 357-368 (Pubitemid 351430366)
14. Croce, M., Orengo, A. M., Azzarone, B., and Ferrini, S. (2012) Immunotherapeutic applications of IL-15. Immunotherapy 4, 957-969
15. Waldmann, T. A. (2006) The biology of interleukin-2 and interleukin-15. Implications for cancer therapy and vaccine design. Nat. Rev. Immunol. 6, 595-601 (Pubitemid 44134092)
16. Dubois, S., Mariner, J., Waldmann, T. A., and Tagaya, Y. (2002) IL-15Rα recycles and presents IL-15 in trans to neighboring cells. Immunity 17, 537-547 (Pubitemid 35351500)
17. Burkett, P. R., Koka, R., Chien, M., Chai, S., Boone, D. L., and Ma, A. (2004) Coordinate expression and trans presentation of interleukin (IL)-15Rα and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis. J. Exp. Med. 200, 825-834 (Pubitemid 39362919)
18. Koka, R., Burkett, P. R., Chien, M., Chai, S., Chan, F., Lodolce, J. P., Boone, D. L., and Ma, A. (2003) Interleukin (IL)-15Rα-deficient natural killer cells survive in normal but not IL-15Rα-deficient mice. J. Exp. Med. 197, 977-984 (Pubitemid 36523195)
19. Sandau, M. M., Schluns, K. S., Lefrancois, L., and Jameson, S. C. (2004) Cutting edge. Transpresentation of IL-15 by bone marrow-derived cells necessitates expression of IL-15 and IL-15Rα by the same cells. J. Immunol. 173, 6537-6541 (Pubitemid 39541036)
20. Schluns, K. S., Kieper, W. C., Jameson, S. C., and Lefrançois, L. (2000) Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat. Immunol. 1, 426-432
21. Bergamaschi, C., Jalah, R., Kulkarni, V., Rosati, M., Zhang, G. M., Alicea, C., Zolotukhin, A. S., Felber, B. K., and Pavlakis, G. N. (2009) Secretion and biological activity of short signal peptide IL-15 is chaperoned by IL-15 receptor β in vivo. J. Immunol. 183, 3064-3072
22. Bergamaschi, C., Rosati, M., Jalah, R., Valentin, A., Kulkarni, V., Alicea, C., Zhang, G. M., Patel, V., Felber, B. K., and Pavlakis, G. N. (2008) Intracellular interaction of interleukin-15 with its receptor β during production leads to mutual stabilization and increased bioactivity. J. Biol. Chem. 283, 4189-4199
23. Bergamaschi, C., Bear, J., Rosati, M., Beach, R. K., Alicea, C., Sowder, R., Chertova, E., Rosenberg, S. A., Felber, B. K., and Pavlakis, G. N. (2012) Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum. Blood 120, e1-8
24. Mortier, E., Woo, T., Advincula, R., Gozalo, S., and Ma, A. (2008) IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J. Exp. Med. 205, 1213-1225 (Pubitemid 351679694)
25. Rubinstein, M. P., Kadima, A. N., Salem, M. L., Nguyen, C. L., Gillanders, W. E., and Cole, D. J. (2002) Systemic administration of IL-15 augments the antigen-specific primary CD8+ T cell response following vaccination with peptide-pulsed dendritic cells. J. Immunol. 169, 4928-4935 (Pubitemid 35217158)
26. Dudley, M. E., Yang, J. C., Sherry, R., Hughes, M. S., Royal, R., Kammula, U., Robbins, P. F., Huang, J., Citrin, D. E., Leitman, S. F., Wunderlich, J., Restifo, N. P., Thomasian, A., Downey, S. G., Smith, F. O., Klapper, J., Morton, K., Laurencot, C., White, D. E., and Rosenberg, S. A. (2008) Adoptive cell therapy for patients with metastatic melanoma: Evaluation of intensive myeloablative chemoradiation preparative regimens. J. Clin. Oncol. 26, 5233-5239
27. Jalah, R., Rosati, M., Kulkarni, V., Patel, V., Bergamaschi, C., Valentin, A., Zhang, G. M., Sidhu, M. K., Eldridge, J. H., Weiner, D. B., Pavlakis, G. N., and Felber, B. K. (2007) Efficient systemic expression of bioactive IL-15 in mice upon delivery of optimized DNA expression plasmids. DNA Cell Biol. 26, 827-840 (Pubitemid 350274411)
28. Mortier, E., Bernard, J., Plet, A., and Jacques, Y. (2004) Natural, proteolytic release of a soluble form of human IL-15 receptor β-chain that behaves as a specific, high affinity IL-15 antagonist. J. Immunol. 173, 1681-1688 (Pubitemid 38971599)
29. Vyas, V. V., Esposito, D., Sumpter, T. L., Broadt, T. L., Hartley, J., Knapp, G. C., 4th, Cheng, W., Jiang, M. S., Roach, J. M., Yang, X., Giardina, S. L., Mitra, G., Yovandich, J. L., Creekmore, S. P., Waldmann, T. A., and Zhu, J. (2012) Clinical manufacturing of recombinant human interleukin 15. I. Production cell line development and protein expression in E. coli with stop codon optimization. Biotechnol. Prog. 28, 497-507
30. Anderson, D. M., Kumaki, S., Ahdieh, M., Bertles, J., Tometsko, M., Loomis, A., Giri, J., Copeland, N. G., Gilbert, D. J., and Jenkins, N. A. (1995) Functional characterization of the human interleukin-15 receptor-chain and close linkage of IL15RA and IL2RA genes. J. Biol. Chem. 270, 29862-29869 (Pubitemid 26002153)
31. Dubois, S., Magrangeas, F., Lehours, P., Raher, S., Bernard, J., Boisteau, O., Leroy, S., Minvielle, S., Godard, A., and Jacques, Y. (1999) Natural splicing of exon 2 of human interleukin-15 receptor β-chain mRNA results in a shortened form with a distinct pattern of expression. J. Biol. Chem. 274, 26978-26984
32. Picker, L. J., Reed-Inderbitzin, E. F., Hagen, S. I., Edgar, J. B., Hansen, S. G., Legasse, A., Planer, S., Piatak, M., Jr., Lifson, J. D., Maino, V. C., Axthelm, M. K., and Villinger, F. (2006) IL-15 induces CD4 effector memory T cell production and tissue emigration in nonhuman primates. J. Clin. Invest. 116, 1514-1524
33. Berger, C., Berger, M., Hackman, R. C., Gough, M., Elliott, C., Jensen, M. C., and Riddell, S. R. (2009) Safety and immunologic effects of IL-15 administration in nonhuman primates. Blood 114, 2417-2426
34. Lugli, E., Goldman, C. K., Perera, L. P., Smedley, J., Pung, R., Yovandich, J. L., Creekmore, S. P., Waldmann, T. A., and Roederer, M. (2010) Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates. Blood 116, 3238-3248
35. Sneller, M. C., Kopp, W. C., Engelke, K. J., Yovandich, J. L., Creekmore, S. P., Waldmann, T. A., and Lane, H. C. (2011) IL-15 administered by continuous infusion to rhesus macaques induces massive expansion of CD8+ T effector memory population in peripheral blood. Blood 118, 6845-6848
36. Waldmann, T. A., Lugli, E., Roederer, M., Perera, L. P., Smedley, J. V., Macallister, R. P., Goldman, C. K., Bryant, B. R., Decker, J. M., Fleisher, T. A., Lane, H. C., Sneller, M. C., Kurlander, R. J., Kleiner, D. E., Pletcher, J. M., Figg, W. D., Yovandich, J. L., and Creekmore, S. P. (2011) Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques. Blood 117, 4787-4795
37. Bamford, R. N., DeFilippis, A. P., Azimi, N., Kurys, G., and Waldmann, T. A. (1998) The 5' untranslated region, signal peptide, and the coding sequence of the carboxyl terminus of IL-15 participate in its multifaceted translational control. J. Immunol. 160, 4418-4426 (Pubitemid 28217299)
38. Onu, A., Pohl, T., Krause, H., and Bulfone-Paus, S. (1997) Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms. J. Immunol. 158, 255-262 (Pubitemid 127483863)
39. Tagaya, Y., Bamford, R. N., DeFilippis, A. P., and Waldmann, T. A. (1996) IL-15. A pleiotropic cytokine with diverse receptor/signaling pathways whose expression is controlled at multiple levels. Immunity 4, 329-336 (Pubitemid 26174048)
40. Tagaya, Y., Kurys, G., Thies, T. A., Losi, J. M., Azimi, N., Hanover, J. A., Bamford, R. N., and Waldmann, T. A. (1997) Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides. Proc. Natl. Acad. Sci. U.S.A. 94, 14444-14449 (Pubitemid 28041393)
41. Waldmann, T. A., and Tagaya, Y. (1999) The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu. Rev. Immunol. 17, 19-49 (Pubitemid 29241118)
42. Duitman, E. H., Orinska, Z., Bulanova, E., Paus, R., and Bulfone-Paus, S. (2008) How a cytokine is chaperoned through the secretory pathway by complexing with its own receptor. Lessons from interleukin-15 (IL-15)/ IL-15 receptor β. Mol. Cell. Biol. 28, 4851-4861
43. Giri, J. G., Kumaki, S., Ahdieh, M., Friend, D. J., Loomis, A., Shanebeck, K., DuBose, R., Cosman, D., Park, L. S., and Anderson, D. M. (1995) Identification and cloning of a novel IL-15 binding protein that is structurally related to the-chain of the IL-2 receptor. EMBO J. 14, 3654-3663
44. Kurys, G., Tagaya, Y., Bamford, R., Hanover, J. A., and Waldmann, T. A. (2000) The long signal peptide isoform and its alternative processing direct the intracellular trafficking of interleukin-15. J. Biol. Chem. 275, 30653-30659
45. Solá, R. J., and Griebenow, K. (2009) Effects of glycosylation on the stability of protein pharmaceuticals. J. Pharm. Sci. 98, 1223-1245
46. Chamorey, A. L., Magné, N., Pivot, X., and Milano, G. (2002) Impact of glycosylation on the effect of cytokines. A special focus on oncology. Eur. Cytokine Netw. 13, 154-160 (Pubitemid 34747916)
47. Karpusas, M., Whitty, A., Runkel, L., and Hochman, P. (1998) The structure of human interferon-β. Implications for activity. Cell Mol. Life Sci. 54, 1203-1216 (Pubitemid 28529112)
48. Takeuchi, M., and Kobata, A. (1991) Structures and functional roles of the sugar chains of human erythropoietins. Glycobiology 1, 337-346
49. Gribben, J. G., Devereux, S., Thomas, N. S., Keim, M., Jones, H. M., Goldstone, A. H., and Linch, D. C. (1990) Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF. Lancet 335, 434-437 (Pubitemid 20054650)
50. Querol, S., Cancelas, J. A., Amat, L., Capmany, G., and Garcia, J. (1999) Effect of glycosylation of recombinant human granulocytic colony-stimulating factor on expansion cultures of umbilical cord blood CD34+ cells. Haematologica 84, 493-498 (Pubitemid 29323256)
51. Beq, S., Rozlan, S., Gautier, D., Parker, R., Mersseman, V., Schilte, C., Assouline, B., Rancé, I., Lavedan, P., Morre, M., and Cheynier, R. (2009) Injection of glycosylated recombinant simian IL-7 provokes rapid and massive T-cell homing in rhesus macaques. Blood 114, 816-825
52. McElroy, C. A., Dohm, J. A., and Walsh, S. T. (2009) Structural and biophysical studies of the human IL-7/IL-7Rα complex. Structure 17, 54-65
53. Rosenberg, S. A., Sportès, C., Ahmadzadeh, M., Fry, T. J., Ngo, L. T., Schwarz, S. L., Stetler-Stevenson, M., Morton, K. E., Mavroukakis, S. A., Morre, M., Buffet, R., Mackall, C. L., and Gress, R. E. (2006) IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J. Immunother. 29, 313-319 (Pubitemid 44297299)
54. Perales, M. A., Goldberg, J. D., Yuan, J., Koehne, G., Lechner, L., Papadopoulos, E. B., Young, J. W., Jakubowski, A. A., Zaidi, B., Gallardo, H., Liu, C., Rasalan, T., Wolchok, J. D., Croughs, T., Morre, M., Devlin, S. M., and van den Brink, M. R. (2012) Recombinant human interleukin-7 (CYT107) promotes T cell recovery following allogeneic stem cell transplantation. Blood 120, 4882-4891
55. Chirifu, M., Hayashi, C., Nakamura, T., Toma, S., Shuto, T., Kai, H., Yamagata, Y., Davis, S. J., and Ikemizu, S. (2007) Crystal structure of the IL-15-IL-15Rα complex, a cytokine-receptor unit presented in trans. Nat. Immunol. 8, 1001-1007 (Pubitemid 47300015)
56. Ring, A. M., Lin, J. X., Feng, D., Mitra, S., Rickert, M., Bowman, G. R., Pande, V. S., Li, P., Moraga, I., Spolski, R., Ozkan, E., Leonard, W. J., and Garcia, K. C. (2012) Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat. Immunol. 13, 1187-1195
57. Han, K. P., Zhu, X., Liu, B., Jeng, E., Kong, L., Yovandich, J. L., Vyas, V. V., Marcus, W. D., Chavaillaz, P. A., Romero, C. A., Rhode, P. R., and Wong, H. C. (2011) IL-15:IL-15 receptor β superagonist complex. High-level coexpression in recombinant mammalian cells, purification and characterization. Cytokine 56, 804-810
58. DePaolo, R. W., Abadie, V., Tang, F., Fehlner-Peach, H., Hall, J. A., Wang, W., Marietta, E. V., Kasarda, D. D., Waldmann, T. A., Murray, J. A., Semrad, C., Kupfer, S. S., Belkaid, Y., Guandalini, S., and Jabri, B. (2011) Coadjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 471, 220-224
59. Gonzalez-Alvaro, I., Ortiz, A. M., Garcia-Vicuña, R., Balsa, A., Pascual-Salcedo, D., and Laffon, A. (2003) Increased serum levels of interleukin-15 in rheumatoid arthritis with long-term disease. Clin. Exp. Rheumatol. 21, 639-642 (Pubitemid 37236459)
60. Rentzos, M., Cambouri, C., Rombos, A., Nikolaou, C., Anagnostouli, M., Tsoutsou, A., Dimitrakopoulos, A., Triantafyllou, N., and Vassilopoulos, D. (2006) IL-15 is elevated in serum and cerebrospinal fluid of patients with multiple sclerosis. J. Neurol. Sci. 241, 25-29 (Pubitemid 43112512)