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Interleukin-21: biology and application to cancer therapy

, MD & , MD
Pages 1295-1307 | Published online: 11 Aug 2008

Bibliography

  • Parrish-Novak J, Dillon SR, Nelson A, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 2000;408(6808):57-63
  • Dumoutier L, Van Roost E, Colau D, Renauld JC. Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor. Proc Natl Acad Sci USA 2000;97(18):10144-9
  • Mehta DS, Wurster AL, Grusby MJ. Biology of IL-21 and the IL-21 receptor. Immunol Rev 2004;202:84-95
  • Spolski R, Leonard WJ. Interleukin-21: basic biology and implications for cancer and autoimmunity. Ann Rev Immunol 2008;26:57-79
  • Chtanova T, Tangye SG, Newton R, et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol 2004;173(1):68-78
  • Wurster AL, Rodgers VL, Satoskar AR, et al. Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon γ-producing Th1 cells. J Exp Med 2002;196(7):969-77
  • Korn T, Bettelli E, Gao W, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 2007;448(7152):484-7
  • Nurieva R, Yang XO, Martinez G, et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007;448(7152):480-3
  • Kasaian MT, Whitters MJ, Carter LL, et al. IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity. Immunity 2002;16(4):559-69
  • Zeng R, Spolski R, Finkelstein SE, et al. Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J Exp Med 2005;201(1):139-48
  • Ozaki K, Spolski R, Feng CG, et al. A critical role for IL-21 in regulating immunoglobulin production. Science 2002;298(5598):1630-4
  • Sivori S, Cantoni C, Parolini S, et al. IL-21 induces both rapid maturation of human CD34+ cell precursors towards NK cells and acquisition of surface killer Ig-like receptors. Eur J Immunol 2003;33(12):3439-47
  • Strengell M, Matikainen S, Siren J, et al. IL-21 in synergy with IL-15 or IL-18 enhances IFN-γ production in human NK and T cells. J Immunol 2003;170(11):5464-9
  • Leonard WJ, Spolski R. Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol 2005;5(9):688-98
  • Coquet JM, Kyparissoudis K, Pellicci DG, et al. IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production. J Immunol 2007;178(5):2827-34
  • Godfrey DI, Kronenberg M. Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 2004;114(10):1379-88
  • Barker BR, Parvani JG, Meyer D, et al. IL-21 induces apoptosis of antigen-specific CD8+ T lymphocytes. J Immunol 2007;179(6):3596-603
  • Li Y, Yee C. IL-21 mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes. Blood 2008;111(1):229-35
  • Li Y, Bleakley M, Yee C. IL-21 influences the frequency, phenotype, and affinity of the antigen-specific CD8 T cell response. J Immunol 2005;175(4):2261-9
  • Liu S, Lizee G, Lou Y, et al. IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells. Int Immunol 2007;19(10):1213-21
  • Ozaki K, Spolski R, Ettinger R, et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol 2004;173(9):5361-71
  • Mehta DS, Wurster AL, Whitters MJ, et al. MJ. IL-21 induces the apoptosis of resting and activated primary B cells. J Immunol 2003;170(8):4111-8
  • Jin H, Carrio R, Yu A, Malek TR. Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis. J Immunol 2004;173(1):657-65
  • Ugai S, Shimozato O, Kawamura K, et al. Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts. Cancer Gene Ther 2003;10(3):187-92
  • Ma HL, Whitters MJ, Konz RF, et al. IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-γ. J Immunol 2003;171(2):608-15
  • Di Carlo E, Comes A, Orengo AM, et al. IL-21 induces tumor rejection by specific CTL and IFN-γ-dependent CXC chemokines in syngeneic mice. J Immunol 2004;172(3):1540-7
  • Furukawa J, Hara I, Nagai H, et al. Interleukin-21 gene transfection into mouse bladder cancer cells results in tumor rejection through the cytotoxic T lymphocyte response. J Urol 2006;176(3):1198-203
  • Daga A, Orengo AM, Gangemi RM, et al. Glioma immunotherapy by IL-21 gene-modified cells or by recombinant IL-21 involves antibody responses. Int J Cancer 2007;121(8):1756-63
  • Kumano M, Hara I, Furukawa J, et al. Interleukin-21 Activates cytotoxic T lymphocytes and natural killer cells to generate antitumor response in mouse renal cell carcinoma. J Urol 2007;178:1504-9
  • Croce M, Meazza R, Orengo AM, et al. Immunotherapy of neuroblastoma by an interleukin-21-secreting cell vaccine involves survivin as antigen. Cancer Immunol Immunother 2008
  • Comes A, Rosso O, Orengo AM, et al. CD25+ regulatory T cell depletion augments immunotherapy of micrometastases by an IL-21-secreting cellular vaccine. J Immunol 2006;176(3):1750-8
  • He H, Wisner P, Yang G, et al. Combined IL-21 and low-dose IL-2 therapy induces anti-tumor immunity and long-term curative effects in a murine melanoma tumor model. J Transl Med 2006;4:24
  • Kirkwood JM, Manola J, Ibrahim J, et al. A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res 2004;10(5):1670-7
  • Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999;17(7):2105-16
  • Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995;13(3):688-96
  • Wang G, Tschoi M, Spolski R, et al. In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res 2003;63(24):9016-22
  • Moroz A, Eppolito C, Li Q, et al. IL-21 enhances and sustains CD8+ T cell responses to achieve durable tumor immunity: comparative evaluation of IL-2, IL-15, and IL-21. J Immunol 2004;173(2):900-9
  • Cartron G, Watier H, Golay J, Solal-Celigny P. From the bench to the bedside: ways to improve rituximab efficacy. Blood 2004;104(9):2635-42
  • Zhang W, Gordon M, Schultheis AM, et al. FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol 2007;25(24):3712-8
  • Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 2000;6(4):443-6
  • Roda JM, Parihar R, Lehman A, et al. Interleukin-21 enhances NK cell activation in response to antibody-coated targets. J Immunol 2006;177(1):120-9
  • Roda JM, Joshi T, Butchar JP, et al. The activation of natural killer cell effector functions by cetuximab-coated, epidermal growth factor receptor positive tumor cells is enhanced by cytokines. Clin Cancer Res 2007;13(21):6419-28
  • Sondergaard H, Frederiksen KS, Thygesen P, et al. Interleukin 21 therapy increases the density of tumor infiltrating CD8+ T cells and inhibits the growth of syngeneic tumors. Cancer Immunol Immunother 2007;56(9):1417-28
  • Wang HY, Wang RF. Regulatory T cells and cancer. Curr Opin Immunol 2007;19(2):217-23
  • Peluso I, Fantini MC, Fina D, et al. IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes. J Immunol 2007;178(2):732-9
  • Ozaki K, Kikly K, Michalovich D, et al. Cloning of a type I cytokine receptor most related to the IL-2 receptor β chain. Proc Natl Acad Sci USA 2000;97(21):11439-44
  • De Totero D, Meazza R, Zupo S, et al. Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells. Blood 2006;107(9):3708-15
  • 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(2):517-24
  • Jahrsdorfer B, Blackwell SE, Wooldridge JE, et al. B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation. Blood 2006;108(8):2712-9
  • Roda JM, Gowda A, Hussain R, et al. IL-21 promotes apoptosis through induction of the BH3 only protein Bim and enhances direct and innate immune-promoted death of chronic lymphocytic leukemia cells. Blood 2007;110(11):3118
  • Gowda A, Roda J, Hussain SR, et al. IL-21 mediates apoptosis through up-regulation of the BH3 family member BIM and enhances both direct and antibody dependent cellular cytotoxicity in primary chronic lymphocytic cells. Blood 2008;111(9):4723-30
  • Akamatsu N, Yamada Y, Hasegawa H, et al. High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma. Cancer Lett 2007;256(2):196-206
  • Sarosiek KA, Chen J, Pham DG, et al. Interleukin-21-induced apoptosis and cell death of diffuse large B-cell lymphoma (DLBCL) cell lines and primary tumors are associated with an induction of Bim. ASH Annual Meeting Abstracts. 2006;108(11):2503
  • Marzec M, Halasa K, Kasprzycka M, et al. Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells. Cancer Res 2008;68(4):1083-91
  • Yoon JS, Newton SM, Wysocka M, et al. IL-21 enhances antitumor responses without stimulating proliferation of malignant T cells of patients with Sezary syndrome. J Invest Dermatol 2008;128(2):473-80
  • Brenne AT, Ro TB, Waage A, et al. Interleukin-21 is a growth and survival factor for human myeloma cells. Blood 2002;99(10):3756-62
  • Ueda M, Imada K, Imura A, et al. Expression of functional interleukin-21 receptor on adult T-cell leukaemia cells. Br J Haematol 2005;128(2):169-76
  • Davis ID, Skrumsager BK, Cebon J, et al. An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma. Clin Cancer Res 2007;13(12):3630-6
  • Thompson JA, Curti BD, Redman BG, et al. Phase I study of recombinant interleukin-21 in patients with metastatic melanoma and renal cell carcinoma. J Clin Oncol 2008;26(12):2034-9
  • Frederiksen KS, Lundsgaard D, Freeman JA, et al. IL-21 induces in vivo immune activation of NK cells and CD8(+) T cells in patients with metastatic melanoma and renal cell carcinoma. Cancer Immunol Immunother 2008: published online 20 Feb 2008, doi:10.1007/s00262-008-0479-4
  • Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 2002;99(3):754-8
  • Weng WK, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 2003;21(21):3940-7
  • Kindsvogel W, Hughes S, Bannink K, et al. IL-21 enhances rituximab-mediated killing of B-lymphoma cell lines in vitro and in vivo. J Clin Oncol 2004;22(14S):2581
  • Hughes SD, Ponce RA, Krejsa C, et al. IL-21 Improves rituximab-mediated B cell depletion. ASH Annual Meeting Abstracts. Blood 2005;106(11):345
  • Timmerman JM, Byrd JC, Andorsky DJ, et al. Recombinant interleukin-21 plus rituximab: clinical activity in a phase 1, dose-finding trial in relapsed low-grade B Cell lymphoma. ASH Annual Meeting Abstracts. Blood 2007;110(11):2577
  • Timmerman JM, Byrd JC, Andorsky DJ, et al. Efficacy and safety of recombinant interleukin-21 (rIL-21) and rituximab in relapsed/refractory indolent lymphoma [abstract 8554]. J Clin Oncol 2008;26(Suppl)
  • Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115-24
  • Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356(2):125-34
  • Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356(22):2271-81
  • Musolino A, Naldi N, Bortesi B, et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 2008;26(11):1789-96
  • Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med 2004;10(9):909-15
  • Morgan RA, Dudley ME, Wunderlich JR, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006;314(5796):126-9
  • Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005;23(10):2346-57
  • Davis ID, Brady B, Kefford R, et al. Activity of recombinant human interleukin-21 (rIL-21) in patients (pts) with stage IV malignant melanoma (MM) without prior treatment: Clinical data from a phase IIa study. J Clin Oncol 2008;26(Suppl) [abstract 3042]
  • Schmidt H, Selby P, Mouritzen U, et al. Subcutaneous (SC) dosing of recombinant human interleukin-21 (rIL-21) is safe and has clinical activity: Results from a dose-escalation study in stage 4 melanoma (MM) or renal cell cancer (RCC). J Clin Oncol 2008;26(Suppl) [abstract 3041]
  • Bhatia S, Curti BD, Gordon MS, et al. Recombinant IL-21 (rIL-21) in combination with sorafenib: Interim results from a phase 1/2 study in patients with metastatic renal cell cancer (mRCC).J Clin Oncol 2008;26(Suppl) [abstract 16008]

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