The biology of interleukin-2 and interleukin-15: Implications for cancer therapy and vaccine design

Nature Reviews Immunology

Volumn 6, Issue 8, 2006, Pages 595-601

  Waldmann, Thomas A ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BASILIXIMAB; DACLIZUMAB; INTERLEUKIN 15; INTERLEUKIN 2; VACCINE;

AUTOIMMUNE DISEASE; CANCER; CLINICAL TRIAL; DRUG EFFICACY; HUMAN; IMMUNOBIOLOGY; IMMUNOTHERAPY; INFECTION; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALS; ANTIBODIES; HUMANS; IMMUNOTHERAPY; INTERLEUKIN-15; INTERLEUKIN-2; NEOPLASMS; RECEPTORS, INTERLEUKIN-15; RECEPTORS, INTERLEUKIN-2; VACCINES;

EID: 33746547247     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1901     Document Type: Review

References (68)

1. Sugamura, K. et al. The interleukin-2 receptor γ chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu. Rev. Immunol. 14, 179-205 (1996).
2. Noguchi, M. et al. Interleukin-2 receptor γ chain: a functional component of the interleukin-7 receptor. Science 262, 1877-1880 (1993).
3. Waldmann, T. A., Dubois, S. & Tagaya, Y. Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 14, 105-110 (2001). This Review provides an analysis of the similarities and differences in the functions of IL-2 and IL-15, as well as the mechanisms that underlie the distinct functions.
4. Waldmann, T. A. & Tagaya, Y. 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 (1999).
5. Fehniger, T. A. & Caligiuri, M. A. Interleukin 15: biology and relevance to human disease. Blood 97, 14-32 (2001). This is an excellent review of IL-15 biology. It discusses the disorders of IL-15 in human diseases and considers the implications of these abnormalities for immunotherapy.
6. Bamford, R. N. et al. The interleukin (IL) 2 receptor β chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc. Natl Acad. Sci. USA 91, 4940-4944 (1994).
7. Grabstein, K. H. et al. Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor. Science 264, 965-968 (1994).
8. Giri, J. C. et al. Identification and cloning of a novel IL-15 binding protein that is structurally related to the α chain of the IL-2 receptor. EMBO J. 14, 3654-3663 (1995).
9. Waldmann, T. A. The interleukin-2 receptor. J. Biol. Chem. 266, 2681-2684 (1991).
10. Taniguchi, T. & Minami, Y. The IL-2/IL-2 receptor system: a current overview. Cell 73, 5-8 (1993).
11. Miyazaki, T. et al. Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc and lck cooperate in hematopoietic cell proliferation. Cell 81, 223-231 (1995).
12. hi memory T cells.
13. + memory T cells by opposing cytokines. Science 288, 675-678 (2000).
14. Marks-Konczalik, J. et al. IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc. Natl Acad. Sci. USA 97, 11445-11450 (2000).
15. Fehniger, T. A., Cooper, M. A. & Caligiuri, M. A. Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine Growth Factor Rev. 13, 169-183 (2002).
16. Carson, W. E. et al. A potential role for interleukin-15 in the regulation of human natural killer cell survival. J. Clin. Invest. 99, 937-943 (1997).
17. Lenardo, M. J. Fas and the art of lymphocyte maintenance. J. Exp. Med. 183, 721-724 (1996).
18. Fontenot, J. D., Rassmussen, J. P., Gavin, M. A. & Rudensky, A. Y. A function for interleukin-2 in FOXP3-expressing regulatory T cells. Nature Immunol. 6, 1142-1151 (2005).
19. + regulatory T cells in the absence of interleukin 2 signaling. Nature Immunol. 6, 1152-1159 (2005).
20. reg cells fit. Nature Immunol. 6, 1071-1072 (2005).
21. + bone marrow-derived cells. Blood 103, 988-994 (2004).
22. Becker, T. C. et al. Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J. Exp. Med. 195, 1541-1548 (2002).
23. Rosenberg, S. A. Interleukin-2 and the development of immunotherapy for the treatment of patients with cancer. Cancer J. Sci. Am. 6, S2-S7 (2000).
24. Waldmann, T. A. et al. The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. Blood 82, 1701-1712 (1993).
25. Morris, J. C. et al. Preclinical and Phase I clinical trial of blockade of IL-15 using Mikβ1 monoclonal antibody in T cell large granular lymphocyte leukemia. Proc. Natl Acad. Sci. USA 103, 401-406 (2006).
26. Waldmann, T. A., Dubois, S., Muller, J., Goldman, C. & Damjanovich, S. in Biophysical Aspects of Transmembrane Signaling (ed. Damjanovich, S.) 97-121 (Springer, Heidelberg, 2005).
27. Schorle, H., Holtschke, T., Hunig, T., Schimpl, A. & Horak, I. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352, 621-624 (1991).
28. Sadlack, B. et al. Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4. Eur. J. Immunol. 24, 281-284 (1994).
29. Lodolce, J. P. et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 9, 669-676 (1998).
30. Kennedy, M. K. et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J. Exp. Med. 191, 771-780 (2000).
31. Kishimoto, T. et al. (eds) Leukocyte typing VI. White Cell Differentiation Antigens (Garland, New York, 1997).
32. Dubois, S. et al. Distinct pathways involving the FK506-binding proteins 12 and 12.6 underlie IL-2 versus IL-15-mediated proliferation of cells. Proc. Natl Acad. Sci. USA 100, 14169-14174 (2003).
33. Bulfone-Paus, S. et al. Death deflected: IL-15 inhibits TNF-α-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Rα chain. FASEB J. 13, 1575-1585 (1999).
34. Damjanovich, S. et al. Preassembly of interleukin 2 (IL-2) receptor subunits on resting Kit 225 K6 T cells and their modulation by IL-2, IL-7, and IL-15: a fluorescence resonance energy transfer study. Proc. Natl Acad. Sci. USA 94, 13134-13139 (1997).
35. hi memory T cells.
36. Lodolce, J. P., Burkett, P. R., Boone, D. L., Chien, M. & Ma, A. T-cell-independent interleukin 15Rα signals are required for bystander proliferation. J. Exp. Med. 194, 1187-1194 (2001).
37. Rosenberg, S. A. et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin-2. JAMA 271, 907-913 (1994).
38. Munger, W. et al. Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2. Cell. Immunol. 165, 289-293 (1995).
39. Evans, R., Fuller, J. A., Christianson, C., Krupke, D. M. & Troutt, A. B. 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. 179, 66-73 (1997).
40. Yajima, T. et al. Overexpression of interleukin-15 in vivo enhances antitumor activity against MHC class I-negative and -positive malignant melanoma through augmented NK activity and cytotoxic T-cell response. Int. J. Cancer 99, 573-578 (2002).
41. Kobayashi, H. et al. 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 (2005).
42. + T-cell-mediated immunity, whereas vaccines incorporating IL-2 elicited short-lived immunity.
43. + T cells. Proc. Natl Acad. Sci. USA 101, 15154-15159 (2004).
44. Kutzler, M. A. 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. 175, 112-123 (2005).
45. Nashan, B. et al. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Croup. Lancet 350, 1193-1198 (1997).
46. Kirkman, R. L. et al. A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation. Transplantation 51, 107-113 (1991).
47. Vincenti, F. et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N. Engl. J. Med. 338, 161-165 (1998). This report of a Phase III clinical trial of daclizumab shows that it is effective for the reduction of acute renal-allograft rejection episodes in patients receiving a human renal transplant. On the basis of this study, the FDA approved daclizumab for use in renal organ-transplantation protocols.
48. Waldmann, T. A. et al. Radioimmunotherapy of interleukin-2Rα- expressing adult T-cell leukemia with yttrium-90-labeled anti-Tac. Blood 86, 4063-4075 (1995).
49. Nussenblatt, R. B. et al. Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a Phase I/II clinical trial. Proc. Natl Acad. Sci. USA 96, 7462-7466 (1999).
50. Bielekova, B. et al. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon β. Proc. Natl Acad. Sci. USA 101, 8705-8708 (2004). This paper shows that treatment with daclizumab leads to a 78% reduction in new contrast-enhancing lesions in patients with multiple sclerosis who have failed to respond to treatment with IFNβ.
51. Waldmann, T. A. et al. Functional and phenotypic comparison of human T cell leukemia/lymphoma virus positive adult T cell leukemia with human T cell leukemia/lymphoma virus negative Sezary leukemia, and their distinction using anti-Tac. Monoclonal antibody identifying the human receptor for T cell growth factor. J. Clin. Invest. 73, 1711-1718 (1984).
52. Waldmann, T. A. The meandering 45-year odyssey of a clinical immunologist. Annu. Rev. Immunol. 21, 1-27 (2002).
53. McInnes, I. B., Leung, B. P., Sturrock, R. D., Field, M. & Liew, F. Y. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-α production in rheumatoid arthritis. Nature Med. 3, 189-195 (1997). This study found that IL-15 effectively induces TNF production in patients with rheumatoid arthritis, through a process that requires the interaction of synovial cells and T cells.
54. Azimi, N., Nagai, M., Jacobson, S. & Waldmann, T. A. IL-15 plays a major role in the persistence of Tax-specific CD8 cells in HAM/TSP patients. Proc. Natl Acad. Sci. USA 98, 14559-14564 (2001).
55. Ruchatz, H., Leung, B. P., Wei, X. Q., McInnes, I. B. & Liew, F. Y. Soluble IL-15 receptor α-chain administration prevents murine collagen-induced arthritis: a role for IL-15 in development of antigen-induced immunopathology. J. Immunol. 160, 5654-5660 (1998).
56. Kim, Y. S. et al. Targeting the IL-15 receptor with an antagonist IL-15 mutant/Fcγ2a protein blocks delayed-type hypersensitivity. J. Immunol. 160, 5742-5748 (1998).
57. Baslund, B. et al. Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum. 52, 2686-2692 (2005).
58. Villadsen, L. S. et al. Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model. J. Clin. Invest. 112, 1571-1580 (2003).
59. Mention, J. J. et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 125, 730-745 (2003).
60. Harada, S. et al. Production of interleukin-7 and interleukin-15 by fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum. 42, 1508-1516 (1999).
61. Oppenheimer-Marks, N., Brezinschek, R. I., Mohamadzadeh, M., Vita, R. & Lipsky, P. E. Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells in vitro and in the SCID mouse-human rheumatoid arthritis model in vivo. J. Clin. Invest. 101, 1261-1272 (1998).
62. Losy, J., Niezgoda, A. & Zaremba, J. IL-15 is elevated in sera of patients with relapsing-remitting multiple sclerosis. Folia Neuropathol. 40, 151-153 (2002).
63. Meresse, B. et al. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21, 357-366 (2004).
64. Feldmann, M., Brennan, F. M. & Maini, R. N. Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14, 397-440 (1996).
65. Guex-Crosier, Y. et al. Humanized antibodies against the α-chain of the IL-2 receptor and against the β-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases. J. Immunol. 158, 452-458 (1997).
66. Hakimi, J. et al. Humanized Mikβ1, a humanized antibody to the IL-2 receptor β-chain that acts synergistically with humanized anti-TAC. J. Immunol. 151, 1075-1085 (1993).
67. Tinubu, S. A. et al. Humanized antibody directed to the IL-2 receptor β-chain prolongs primate cardiac allograft survival. J. Immunol. 153, 4330-4338 (1994).
68. Leonard, W. J. in Cytokine Reference Vol. 2 (eds Oppenheim, J. J. & Feldmann, M.) 1439-1457 (Academic, San Diego, 2001).