Interleukin-15 in the treatment of cancer

References

• Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science 2013;342:1432-3
   PubMed Web of Science ®Google Scholar
• Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells: CARS take the front seat for hematologic malignancies. Blood 2014;123:2625-35
   PubMed Web of Science ®Google Scholar
• Kochenderfer JN, Dudley ME, Feldman SA, et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 2012;119:2709-20
   PubMed Web of Science ®Google Scholar
• Waldmann TA, Morris JC. Development of antibodies and chimeric molecules for cancer immunotherapy. Adv Immunol 2006;90:83-131
   PubMed Web of Science ®Google Scholar
• Hodi FS, O’Day SJ, McDemott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443-54
   PubMed Web of Science ®Google Scholar
• Rosenberg SA, Yang JC, Topalian SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin-2. JAMA 1994;271:907-13
   PubMed Web of Science ®Google Scholar
• Lenardo MJ. Fas and the art of lymphocyte maintenance. J Exp Med 1996;183:721-4
   PubMed Web of Science ®Google Scholar
• Maloy KJ, Powrie F. Fueling regulation: IL-2 keeps CD4+ Treg cells fit. Nat Immunol 2005;6:1071-2
   PubMed Web of Science ®Google Scholar
• Waldmann TA. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol 2006;6:595-601
   PubMed Web of Science ®Google Scholar
• Fehniger TA, Cooper MA, Caligiuri MA. Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine and Growth Factor Rev 2002;13:169-83
   PubMed Web of Science ®Google Scholar
• Mishra A, Sullivan L, Caligiuri MA. Molecular pathways: interleukin-15 signaling in health and in cancer. Clin Cancer Res 2014;20:2044-50
   PubMed Web of Science ®Google Scholar
• Steel JC, Waldmann TA, Morris JC. Interleukin-15 biology and its therapeutic implications in cancer. Trends Pharmacol Sci 2012;33:35-41
   PubMed Web of Science ®Google Scholar
• Klebanoff CA, Finkelstein SE, Surman DR, et al. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci USA 2004;101:1969-74
   PubMed Web of Science ®Google Scholar
• Waldmann TA, Dubois S, Tagaya Y. Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 2001;14:105-10
   PubMed Web of Science ®Google Scholar
• Armitage RJ, Macduff BM, Eisenman J, et al. IL-15 has stimulatory activity for the induction of B cell proliferation and differentiation. J Immunol 1995;154:483-90
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Zhang X, Sun S, Hwang I, et al. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 1998;8:591-9
   PubMed Web of Science ®Google Scholar
• Lugli E, Dominguez MH, Gattinoni L, et al. Superior T memory stem cell persistence supports long-lived T cell memory. J Clin Invest 2013;123:594-9
   PubMed Web of Science ®Google Scholar
• 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 USA 2000;97:11445-50
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Bamford RN, Grant AJ, Burton JD, et al. The interleukin (IL)2 receptor beta 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 1994;91:4940-4
   PubMed Web of Science ®Google Scholar
• Burton JD, Bamford RN, Peters C, et al. A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci USA 1994;91:4935-9
   PubMed Web of Science ®Google Scholar
• 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 USA 1997;94:14444-9
   PubMed Web of Science ®Google Scholar
• Bamford RN, Battiata AP, Burton JD, et al. Interleukin (IL)15/IL-T production by the adult T-cell leukemia cell line HuT-102 is associated with a human T-cell lymphotrophic virus type I R region/IL-15 fusion message that lacks many upstream AUGs that normally attenuate IL-15 mRNA translation. Proc Natl Acad Sci USA 1996;93:2897-902
   PubMed Web of Science ®Google Scholar
• Bamford RN, DeFilippis AP, Azimi N. 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 1998;160:4418-26
   PubMed Web of Science ®Google Scholar
• Waldmann TA, Tagaya Y. Cytokine reference. Volume I Academic Press; London: 2000. p. 213-24
   Google Scholar
• Anderson DM, Kumaki S, Ahdieh M, et al. Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL-15RA and IL-2RA genes. J Biol Chem 1995;270:29862-9
   PubMed Web of Science ®Google Scholar
• Lucas M, Schachterle W, Oberle K, et al. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 2007;26:503-17
   PubMed Web of Science ®Google Scholar
• McInnes IB, Leung BP, Sturrock RD, et al. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. Nat Med 1997;3:189-95
   PubMed Web of Science ®Google Scholar
• Mueller JR, Waldmann TA, Kruhlak MJ, et al. Paracrine and transpresentation functions of IL-15 are mediated by diverse splice versions of IL-15R alpha in human monocytes and dendritic cells. J Biol Chem 2012;287:40328-38
   PubMed Web of Science ®Google Scholar
• Dubois S, Magrangeas F, Lehours P, et al. Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression. J Biol Chem 1999;274:26978-84
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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 USA 1995;92:8705-9
   PubMed Web of Science ®Google Scholar
• Carson WE, Giri JG, Lindemann MJ, et al. Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med 1994;180:1395-403
   PubMed Web of Science ®Google Scholar
• Sadlack B, Kühn R, Schorle H, et al. Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and-4. Eur J Immunol 1994;24:281-4
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Lebrec H, Horner MJ, Gorski KS, et al. Homeostasis of human NK cells is not IL-15 dependent. J Immunol 2013;191:5551-8
   PubMed Web of Science ®Google Scholar
• Ellery JM, Nicholls PJ. Alternate signalling pathways from the interleukin-2 receptor. Cytokine Growth Factor Rev 2002;13:27-40
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Pelletier M, Ratthé C, Girard D. Mechanisms involved in interleukin-15-induced suppression of human neutrophil apoptosis: role of the anti-apoptotic Mcl-1 protein and several kinases including Janus kinase-2, p38 mitogen-activated protein kinase and extracellular signal-regulated kinases-1/2. FEBS Lett 2002;532:164-70
   PubMed Web of Science ®Google Scholar
• Sathe P, Delconte RB, Souza-Fonseca-Guimaraes F, et al. Innate immunodeficiency following gentic ablation of MCl1 in natural killer cells. Nat Commun 2014;5:4539
   PubMed Web of Science ®Google Scholar
• Dubois S, Mariner J, Waldmann TA, et al. IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells. Immunity 2002;17:537-47
   PubMed Web of Science ®Google Scholar
• Ma A, Koka R, Burkett P. Diverse functions of IL-2, IL-15 and IL-7 in lymphoid homeostasis. Annu Rev Immunol 2006;24:657-79
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Schluns KS, Klonowski KD, Lefrancois L. Transregulation of memory CD8 T-cell proliferation by IL-15Ralpha+ bone marrow-derived cells. Blood 2004;103:988-94
   PubMed Web of Science ®Google Scholar
• Mortier E, Woo T, Advincula R, et al. IL-15R alpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med 2008;205:1213-25
   PubMed Web of Science ®Google Scholar
• Chirifu M, Hayashi C, Nakamura T, et al. Crystal structure of the IL-15-IL-15R alpha complex, a cytoine-receptor unit presented in trans. Nat Immunol 2007;8:1001-7
   PubMed Web of Science ®Google Scholar
• Marcais A, Cherfils-Vicini J, Viant C, et al. The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells. Nat Immunol 2014;15:749-57
   PubMed Web of Science ®Google Scholar
• Olsen SK, Ota N, Kishishita S, et al. Crystal structure of the interleukin-15.interleukin-15 receptor alpha complex: insights into tarns and cis presentation. J Biol chem 2007;282:37191-204
   PubMed Web of Science ®Google Scholar
• Rowley J, Monie A, Hung C-F, Wu TC. Expression of IL-15RA or an IL-15/IL-15RA fusion on CD8+ T cells modifies adoptively transferred T-cell function in cis. Eur J Immunol 2009;39:491-506
   PubMed Web of Science ®Google Scholar
• Waldmann TA, Conlon KC, Stewart DM, et al. Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-Beta-1 mAb in patients with T-cell large granular lymphocytic leukemia. Blood 2013;121:476-84
   PubMed Web of Science ®Google Scholar
• Oh S, Perera LP, Burke DS, et al. IL-15/IL-15R alpha-mediated avidity maturation of memory CD8+ T cells. Proc Natl Acad Sci USA 2004;101:15154-9
   PubMed Web of Science ®Google Scholar
• Ota N, Takase M, Uchiyama H, et al. No requirement of trans presentations of IL-15 for human CD8 T cell proliferation. J Immunol 2010;185:6041-8
   PubMed Web of Science ®Google Scholar
• Zanoni I, Spreafico R, Bodio C, et al. IL-15 cis presentation is required for optimal NK cell activation in lipopolysaccharide-mediated inflammatory conditions. Cell Rep 2013;4:1235-49
   PubMed Web of Science ®Google Scholar
• Chenoweth MJ, Mian MF, Barra NG, et al. IL-15 can signal via IL-15R alpha, JNK, and NF-kB to drive RANTES production by myeloid cells. J Immunol 2012;188:4149-57
   PubMed Web of Science ®Google Scholar
• Tagaya Y, Burton JD, Miyamoto Y, Waldmann TA. Identification of a novel receptor signal transduction pathway for IL-15/T in mast cells. Embo 1996;15:4928-39
   PubMed Web of Science ®Google Scholar
• Pereno R, Giron-Michel J, Gaggero A, et al. IL-15/IL-15R alpha intracellular trafficking in human melanoma cells and signal transduction through the IL-15R alpha. Oncogene 2000;19:5153-62
   PubMed Web of Science ®Google Scholar
• Bulfone-Paus S, Bulanova E, Budagian V, Paus R. The interleukin-15/interleukin-15 receptor system as a model for juxtacrine and reverse signaling. Bioessays 2006;28:362-77
   PubMed Web of Science ®Google Scholar
• Zhang M, Ju W, Yao Z, et al. Augmented interleukin(IL)-15Ralpha expression by CD40 activation is critical in synergistic CD8 T-cell mediated antitumor activity of anti-CD40 antibody with IL-15 in TRAMP-C2 tumors in mice. J Immunol 2012;188:6156-64
   PubMed Web of Science ®Google Scholar
• Kobayashi H, Dubois S, Sato N, et al. Role of trans-cellular IL-15 transpresentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 2005;105:721-7
   PubMed Web of Science ®Google Scholar
• Munger W, DeJoy SQ, Jeyaseelan R Sr, et al. Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2. Cell Immunol 1995;165:289-93
   PubMed Web of Science ®Google Scholar
• Evans R, Fuller JA, Christianson G, et al. 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
   PubMed Web of Science ®Google Scholar
• 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;201:139-48
   PubMed Web of Science ®Google Scholar
• Dubois S, Patel HJ, Zhang M, et al. Preassociation of IL-15 with IL-15R apha-IgG1-Fc enhances its activity on proliferation of NK and CD8+/CD44high T cells and its antitumor action. J Immunol 2008;180:2099-106
   PubMed Web of Science ®Google Scholar
• Zhang M, Yao Z, Dubois S, et al. Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer. Proc Natl Acad Sci USA 2009;106:7513-18
   PubMed Web of Science ®Google Scholar
• Yu P, Steel JC, Zhang M, et al. Simultaneous inhibition of two regulatory T-cell subsets enhanced Interleukin-15 in a prostate tumor model. Proc Natl Acad Sci USA 2012;109:6187-92
   PubMed Web of Science ®Google Scholar
• Huntington ND, Alves NL, Legrand N, et al. IL-15 transpresentation promotes both human T-cell reconstitution and T-cell-dependent antibody responses in vivo. Proc Natl Acad Sci USA 2011;108:6217-22
   PubMed Web of Science ®Google Scholar
• Huntington ND, Legrand N, Alves NL, et al. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med 2009;206:25-34
   PubMed Web of Science ®Google Scholar
• Bessard A, Sole V, Bouchaud G, et al. High antitumor activity of RLl, an interleukin-15 (IL-15)-IL-15 receptor alpha fusion protein, in metastatic melanoma and colorectal cancer. Mol Cancer Ther 2009;8:2736-45
   PubMed Web of Science ®Google Scholar
• NCI Immunotherapy Agent Workshop July 12, 2007
   Google Scholar
• Mueller YM, Petrovas C, Bojczuk PM, et al. Interleukin-15 increases effector memory CD8+ T cells and NK cells in simian immunodeficiency virus-infected macaques. J Virol 2005;79:4877-85
   PubMed Web of Science ®Google Scholar
• Waldmann TA, Lugli E, Roederer M, 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
   PubMed Web of Science ®Google Scholar
• Lugli E, Goldman CK, Perera LP. Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates. Blood 2010;116:3238-48
   PubMed Web of Science ®Google Scholar
• Sneller MC, Kopp WC, Engelke KJ, et al. IL-15 administered by continuous intravenous infusion to rhesus macaques induces massive expansion of the CD8+ T effector memory population in peripheral blood. Blood 2011;118:6845-8
   PubMed Web of Science ®Google Scholar
• Berger C, Berger M, Hackman RC, et al. Safety and immunological effects of IL-15 administration in nonhuman primates. Blood 2009;114:2417-26
   PubMed Web of Science ®Google Scholar
• Verri WACunha TM, Ferreira SH, et al. IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. Eur J Immunol 2007;37:3373-80
   PubMed Web of Science ®Google Scholar
• A Phase I study of intravenous recombinant human IL-15 in adults with refractory metastatic malignant melanoma and metastatic renal cell cancer. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01021059+&Search=Search
   Google Scholar
• Conlon KC, Lugli E, Welles HC, et al. Redistribution, hyperproliferation, activation of NK and CD8 T cells and cytokine production during first-in-human clinical trial of rhIL-15 in patients with cancer. J Clin Oncol 2014; In press
   PubMed Web of Science ®Google Scholar
• Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Eng J Med 2013;368:1509-18
   PubMed Web of Science ®Google Scholar
• Teachey DT, Rheingold SR, Maude SL, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 2013;121:5154-7
   PubMed Web of Science ®Google Scholar
• Recombinant Interleukin-15 in treating patients with advanced melanoma, kidney cancer, non-small cell lung cancer, or squamous cell head and neck cancer. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01727076+&Search=Search
   Google Scholar
• Morishima C, Sondel PM, Kohrt HEK, et al. CITN11-02 Interim trial results: Subcutaneous administration of recombinant human IL-15 (rhIL-15) is associated with robust expansion of peripheral blood CD56+ NK cells. Abstract for SITC Meeting 2014; In press
   Google Scholar
• Continuous infusion of rhIL-15 for adults with advanced cancer. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01572493&Search=Search
   Google Scholar
• Haploidentical donor natural killer cell infusion with IL-15 in Acute Myelogenous Leukemia (AML). Available from: https://clinicaltrials.gov/ct2/results?term=NCT01385423&Search=Search
   Google Scholar
• Cooley S, Verneris MR, Curtsinger J, et al. Recombinant human IL-15 promotes in vivo expansion of adoptively transferred NK cells in a first-in-human phase I dose escalation study in patients with AML. Blood 2012;120:Meeting abstract 894
   Web of Science ®Google Scholar
• Chen J, Petrus M, Bamford R, et al. Increased serum soluble IL-15R alpha levels in T-cell large granular lymphocyte leukemia. Blood 2012;119:137-43
   PubMed Web of Science ®Google Scholar
• Tinhofer I, Marschitz I, Henn T, et al. Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma. Blood 2000;95:610-18
   PubMed Web of Science ®Google Scholar
• Chertova E, Bergamaschi C, Chertov O, et al. Characterization and favorable in vivo properties of heterodimeric soluble IL-15-IL-15R alpha cytokine compared to IL-15 monomer. J Biol Chem 2013;288:18093-103
   PubMed Web of Science ®Google Scholar
• Altor launches clinical trial of IL-15 superagonist protein complex against metastatic melanoma. Cellular Technology Ltd, 2013. Available from: http://clinicaltrials.pharmaceutical-business-review.com/news/altor-launches-clinical trial
   Google Scholar
• Stoklasek TA, Schluns KS, Lefrancois L. Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol 2006;177:6072-80
   PubMed Web of Science ®Google Scholar
• 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 USA 2006;103:9166-71
   PubMed Web of Science ®Google Scholar
• Burkett PR, Koka R, Chien M, et al. 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
   PubMed Web of Science ®Google Scholar
• 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 by the same cells. J Immunol 2004;173:6537-41
   PubMed Web of Science ®Google Scholar
• Bergamaschi C, Bear J, Rosati M, et al. Circulating IL-15 exists as heterodimeric complex with soluble IL-15R alpha in human and mouse serum. Blood 2012;120:e1-8
   PubMed Web of Science ®Google Scholar
• Oh S, Berzofsky JA, Burke DS, et al. Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity. Proc Natl Acad Sci USA 2003;100:3392-7
   PubMed Web of Science ®Google Scholar
• Roberti MP, Barrio MM, Bravo AI, et al. IL-15 and IL-2 increase Cetuximab-mediated cellular cytotoxicity against triple negative breast cancer cell lines expressing EGFR. Breast Cancer Res Treat 2011;130:465-75
   PubMed Web of Science ®Google Scholar
• Sckisel GD, Bouchlaka MN, Mirsoian A. Cyotkine-based immunotherapy impairs primary T cell immunity (VAC3P.942). Immunology 2014;192:abstract 110
   Web of Science ®Google Scholar
• Vincent M, Teppaz G, Lajoie L. Highly potent anti-CD20-RLI immunocytoine targeting established human B lymphoma in SCID mouse. MAbs 2014;4:1026-37
   Google Scholar
• Lee YH, Ishida Y, Rifa’i M, et al. Essential role of CD8+CD122+ regulatory T cells in the recovery from experimental autoimmune encephalomyelitis. J Immunol 2008;180:825-32
   PubMed Web of Science ®Google Scholar
• Endharti AT, Rifa’I M, Shi Z, et al. Cutting edge: CD8+CD122+ regulatory T cells produce IL-10 to suppress IFN-γ production and proliferation of CD8+ T cells. J Immunol 2005;175:7093-7
   PubMed Web of Science ®Google Scholar
• Yu P, Steel JC, Zhang M, et al. Simultaneous blockade of multiple immune system inhibitory checkpoints enhances antitumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model. Clin Can Res 2010;16:6019-28
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Use of IL-15 after chemotherapy and lymphocyte transfer in metastatic melanoma. Available from: https://clinicaltrials.gov/ct2/results?term=NCT01369888&Search=Search
   Google Scholar