Efficacy and mechanism-of-action of a novel superagonist interleukin-15: Interleukin-15 receptor αSu/Fc fusion complex in syngeneic murine models of multiple myeloma

Cancer Research

Volumn 73, Issue 10, 2013, Pages 3075-3086

  Xu, Wenxin ^a   Jones, Monica ^a   Liu, Bai ^a   Zhu, Xiaoyun ^a   Johnson, Christopher B ^b   Edwards, Ana C ^a   Kong, Lin ^a   Jeng, Emily K ^a   Han, Kaiping ^a   Marcus, Warren D ^a   Rubinstein, Mark P ^b   Rhode, Peter R ^a   Wong, Hing C ^a  

^a ALTOR BIOSCIENCE CORPORATION   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALT 803; ANTINEOPLASTIC AGENT; GAMMA INTERFERON; HERMES ANTIGEN; INTERLEUKIN 15; NATURAL KILLER CELL RECEPTOR NKG2D; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER SURVIVAL; CD8+ T LYMPHOCYTE; CELL EXPANSION; CELL PROLIFERATION; CELL STIMULATION; CELL SURFACE; CELL VIABILITY; CELLULAR SECRETION; CONTROLLED STUDY; DOSE RESPONSE; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; FEMALE; IN VITRO STUDY; IN VIVO STUDY; LOW DRUG DOSE; MEMORY T LYMPHOCYTE; MOLECULAR DYNAMICS; MOUSE; MULTIPLE MYELOMA; NONHUMAN; PRIORITY JOURNAL; SINGLE DRUG DOSE; SURVIVAL RATE; TUMOR XENOGRAFT; UPREGULATION;

ANIMALS; ANTINEOPLASTIC AGENTS; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE, TUMOR; CYTOTOXICITY, IMMUNOLOGIC; FEMALE; IMMUNOLOGIC MEMORY; INTERFERON-GAMMA; INTERLEUKIN-15; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; MULTIPLE MYELOMA; PROTEINS; RECEPTORS, INTERLEUKIN-15;

EID: 84877865939     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-12-2357     Document Type: Article

References (47)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.
2. Blade J, Rosinol L, Cibeira MT, Rovira M, Carreras E. Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. Blood 2010;115:3655-63.
3. Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, et al.Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009;2:36.
4. Palumbo A, Attal M, Roussel M. Shifts in the therapeutic paradigm for patients newly diagnosed with multiple myeloma: Maintenance therapy and overall survival. Clin Cancer Res 2011;17:1253-63.
5. Lonial S, Mitsiades CS, Richardson PG. Treatment options for relapsed and refractory multiple myeloma. Clin Cancer Res 2011; 17:1264-77.
6. Waldmann TA. The biology of interleukin-2 and interleukin-15: Implications for cancer therapy and vaccine design. Nat Rev Immunol 2006;6:595-601. (Pubitemid 44134092)
7. Fehniger TA, Caligiuri MA. Interleukin 15: Biology and relevance to human disease. Blood 2001;97:14-32. (Pubitemid 32061238)
8. Peest D, Leo R, Bloche S, Hein R, Stannat-Kiessling S, Tschechne B, et al. Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma. Br J Haematol 1995;89:328-37.
9. Sanjabi S, Mosaheb MM, Flavell RA. Opposing effects of TGF-beta and IL-15 cytokines control the number of short-lived effector CD8+ T cells. Immunity 2009;31:131-44.
10. Stoklasek TA, Schluns KS, Lefrancois L. Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol 2006; 177:6072-80. (Pubitemid 44628822)
11. 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.
12. Epardaud M, Elpek KG, Rubinstein MP, Yonekura AR, Bellemare-Pelletier A, Bronson R, 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. (Pubitemid 351556298)
13. 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.
14. 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.
15. 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.
16. Yu P, Steel JC, Zhang M, Morris JC, Waitz R, Fasso M, et al. Simultaneous inhibition of two regulatory T-cell subsets enhanced Interleukin-15 efficacy in a prostate tumor model. Proc Natl Acad Sci U S A 2012;109:6187-92.
17. Cheever MA. Twelve immunotherapy drugs that could cure cancers. Immunol Rev 2008;222:357-68. (Pubitemid 351430366)
18. Zhu X, Marcus WD, Xu W, Lee HI, Han K, Egan JO, et al. Novel human interleukin-15 agonists. J Immunol 2009;183:3598-607.
19. Han KP, Zhu X, Liu B, Jeng E, Kong L, Yovandich JL, et al. IL-15:IL-15 receptor alpha superagonist complex: High-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine 2011;56:804-10.
20. Radl J, Croese JW, Zurcher C, Van den Enden-Vieveen MH, de Leeuw AM. Animal model of human disease. Multiple myeloma. Am J Pathol 1988;132:593-7.
21. Waldmann TA, Lugli E, Roederer M, Perera LP, Smedley JV, Macallister RP, et al. Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques. Blood 2011;117:4787-95.
22. 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. (Pubitemid 28264750)
23. Tough DF, Zhang X, Sprent J. An IFN-gamma-dependent pathway controls stimulation of memory phenotype CD8+T cell turnover in vivo by IL-12, IL-18, and IFN-gamma. J Immunol 2001;166:6007-11. (Pubitemid 32440725)
24. Sprent J, Zhang X, Sun S, Tough D. T-cell proliferation in vivo and the role of cytokines. Philos Trans R Soc Lond B Biol Sci 2000;355: 317-22. (Pubitemid 30199473)
25. Tietze JK, Wilkins DE, Sckisel GD, Bouchlaka MN, Alderson KL, Weiss JM, et al. Delineation of antigen-specific and antigen-nonspecific CD8 (+) memory T-cell responses after cytokine-based cancer immunotherapy. Blood 2012;119:3073-83.
26. Berner V, Liu H, Zhou Q, Alderson KL, Sun K, Weiss JM, et al. IFNgamma mediates CD4+ T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy. Nat Med 2007;13: 354-60. (Pubitemid 46376686)
27. Murphy WJ, Welniak L, Back T, Hixon J, Subleski J, Seki N, et al. Synergistic anti-tumor responses after administration of agonistic antibodies to CD40 and IL-2: Coordination of dendritic and CD8+ cell responses. J Immunol 2003;170:2727-33. (Pubitemid 36245667)
28. Soudja SM, Ruiz AL, Marie JC, Lauvau G. Inflammatory monocytes activate memory CD8(+) T and innate NK lymphocytes independent of cognate antigen during microbial pathogen invasion. Immunity 2012; 37:549-62.
29. Manning LS, Chamberlain NL, Leahy MF, Cordingley FT. Assessment of the therapeutic potential of cytokines, cytotoxic drugs and effector cell populations for the treatment of multiple myeloma using the 5T33 murine myeloma model. Immunol Cell Biol 1995;73: 326-32.
30. Nguyen KB, Salazar-Mather TP, Dalod MY, Van Deusen JB, Wei XQ, Liew FY, et al. Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection. J Immunol 2002;169:4279-87. (Pubitemid 35178200)
31. Chang CM, Lo CH, Shih YM, Chen Y, Wu PY, Tsuneyama K, et al. Treatment of hepatocellular carcinoma with adeno-associated virus encoding interleukin-15 superagonist. Hum Gene Ther 2010;21: 611-21.
32. Stoklasek TA, Colpitts SL, Smilowitz HM, Lefraņcois 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.
33. Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: An overview of signals, mechanisms and functions. J Leukoc Biol 2004; 75:163-89. (Pubitemid 38174573)
34. Zhu J, Jankovic D, Oler AJ, Wei G, Sharma S, Hu G, et al. The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses. Immunity 2012;37:660-73.
35. Hou J, Baichwal V, Cao Z. Regulatory elements and transcription factors controlling basal and cytokine-induced expression of the gene encoding intercellular adhesion molecule 1. Proc Natl Acad Sci U S A 1994;91:11641-5. (Pubitemid 24356400)
36. Jesse TL, LaChance R, Iademarco MF, Dean DC. Interferon regulatory factor-2 is a transcriptional activator in muscle where It regulates expression of vascular cell adhesion molecule-1. J Cell Biol 1998; 140:1265-76. (Pubitemid 28128884)
37. Gil MP, Bohn E, O'Guin AK, Ramana CV, Levine B, Stark GR, et al. Biologic consequences of Stat1-independent IFN signaling. Proc Natl Acad Sci U S A 2001;98:6680-5. (Pubitemid 32538276)
38. Taub DD, Lloyd AR, Conlon K, Wang JM, Ortaldo JR, Harada A, et al. Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med 1993;177:1809-14. (Pubitemid 23146150)
39. Rollins BJ, Yoshimura T, Leonard EJ, Pober JS. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol 1990;136:1229-33. (Pubitemid 20210321)
40. Liao F, Rabin RL, Yannelli JR, Koniaris LG, Vanguri P, Farber JM. Human Mig chemokine: Biochemical and functional characterization. J Exp Med 1995;182:1301-14.
41. Taub DD, Conlon K, Lloyd AR, Oppenheim JJ, Kelvin DJ. Preferential migration of activated CD4+ and CD8+ T cells in response to MIP-1 alpha and MIP-1 beta. Science 1993;260:355-8. (Pubitemid 23160144)
42. Appay V, Rowland-Jones SL. RANTES: A versatile and controversial chemokine. Trends Immunol 2001;22:83-7. (Pubitemid 32667526)
43. MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annu Rev Immunol 1997;15:323-50. (Pubitemid 27169284)
44. Bolscher BG, Koenderman L, Tool AT, Stokman PM, Roos D. NADPH: O2 oxidoreductase of human eosinophils in the cell-free system. FEBS Lett 1990;268:269-73. (Pubitemid 20233883)
45. Roos D, Bolscher BG, Weening RS, Verhoeven AJ. Formation of reactive oxygen species by phagocytic cells: Functions and dysfunctions. Acta Paediatr Hung 1988;29:83-91.
46. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm. Nat Immunol 2010;11: 889-96.
47. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010;141:39-51.