Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy

References

• Smith KA. Interleukin-2: inception, impact, and implications. Science 1988;240(4856):1169-76
   PubMed Web of Science ®Google Scholar
• Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity 2010;33(2):153-65
   PubMed Web of Science ®Google Scholar
• Liao W, Lin JX, Leonard WJ. Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 2013;38(1):13-25
   PubMed Web of Science ®Google Scholar
• Wang X, Lupardus P, Laporte SL, Garcia KC. Structural biology of shared cytokine receptors. Annu Rev Immunol 2009;27:29-60
   PubMed Web of Science ®Google Scholar
• Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 1976;193(4257):1007-8
   PubMed Web of Science ®Google Scholar
• Lenardo M, Chan KM, Hornung F, et al. Mature T lymphocyte apoptosis--immune regulation in a dynamic and unpredictable antigenic environment. Annu Rev Immunol 1999;17:221-53
   PubMed Web of Science ®Google Scholar
• Pipkin ME, Sacks JA, Cruz-Guilloty F, et al. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity 2010;32(1):79-90
   PubMed Web of Science ®Google Scholar
• Castro I, Dee MJ, Malek TR. Transient enhanced IL-2R signaling early during priming rapidly amplifies development of functional CD8+ T effector-memory cells. J Immunol 2012;189(9):4321-30
   PubMed Web of Science ®Google Scholar
• Wilson EB, Livingstone AM. Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses. J Immunol 2008;181(11):7445-8
   PubMed Web of Science ®Google Scholar
• Mescher MF, Curtsinger JM, Agarwal P, et al. Signals required for programming effector and memory development by CD8+ T cells. Immunol Rev 2006;211:81-92
   PubMed Web of Science ®Google Scholar
• Kalia V, Sarkar S, Subramaniam S, et al. Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. Immunity 2010;32(1):91-103
   PubMed Web of Science ®Google Scholar
• Sprent J, Surh CD. Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells. Nat Immunol 2011;12(6):478-84
   PubMed Web of Science ®Google Scholar
• Hamilton SE, Schenkel JM, Akue AD, Jameson SC. IL-2 complex treatment can protect naive mice from bacterial and viral infection. J Immunol 2010;185(11):6584-90
   PubMed Web of Science ®Google Scholar
• Kamimura D, Bevan MJ. Naive CD8+ T cells differentiate into protective memory-like cells after IL-2 anti IL-2 complex treatment in vivo. J Exp Med 2007;204(8):1803-12
   PubMed Web of Science ®Google Scholar
• Panelli MC, White R, Foster M, et al. Forecasting the cytokine storm following systemic interleukin (IL)-2 administration. J Transl Med 2004;2(1):17
   PubMedGoogle Scholar
• Lotze MT, Frana LW, Sharrow SO, et al. In vivo administration of purified human interleukin 2. I. Half-life and immunologic effects of the Jurkat cell line-derived interleukin 2. J Immunol 1985;134(1):157-66
   PubMed Web of Science ®Google Scholar
• Donohue JH, Rosenberg SA. The fate of interleukin-2 after in vivo administration. J Immunol 1983;130(5):2203-8
   PubMed Web of Science ®Google Scholar
• Anderson PM, Sorenson MA. Effects of route and formulation on clinical pharmacokinetics of interleukin-2. Clin Pharmacokinet 1994;27(1):19-31
   PubMed Web of Science ®Google Scholar
• Shaker MA, Younes HM. Interleukin-2: evaluation of routes of administration and current delivery systems in cancer therapy. J Pharm Sci 2009;98(7):2268-98
   PubMed Web of Science ®Google Scholar
• Konrad MW, Hemstreet G, Hersh EM, et al. Pharmacokinetics of recombinant interleukin 2 in humans. Cancer Res 1990;50(7):2009-17
   PubMed Web of Science ®Google Scholar
• Lotze MT, Matory YL, Ettinghausen SE, et al. In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J Immunol 1985;135(4):2865-75
   PubMed Web of Science ®Google Scholar
• Tang Q, Adams JY, Penaranda C, et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 2008;28(5):687-97
   PubMed Web of Science ®Google Scholar
• Rosenblum MD, Gratz IK, Paw JS, Abbas AK. Treating human autoimmunity: current practice and future prospects. Sci Transl Med 2012;4(125):125sr121
   Web of Science ®Google Scholar
• Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008;133(5):775-87
   PubMed Web of Science ®Google Scholar
• Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 2009;30(5):636-45
   PubMed Web of Science ®Google Scholar
• Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 2012;30:531-64
   PubMed Web of Science ®Google Scholar
• Levin AM, Bates DL, Ring AM, et al. Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’. Nature 2012;484(7395):529-33
   PubMed Web of Science ®Google Scholar
• Baecher-Allan C, Anderson DE. Immune regulation in tumor-bearing hosts. Curr Opin Immunol 2006;18(2):214-19
   PubMed Web of Science ®Google Scholar
• Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 2010;140(6):845-58
   PubMed Web of Science ®Google Scholar
• Sojka DK, Huang YH, Fowell DJ. Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target. Immunology 2008;124(1):13-22
   PubMed Web of Science ®Google Scholar
• Pandiyan P, Zheng L, Ishihara S, et al. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol 2007;8(12):1353-62
   PubMed Web of Science ®Google Scholar
• Shevach EM. Application of IL-2 therapy to target T regulatory cell function. Trends Immunol 2012;33(12):626-32
   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(12):907-13
   PubMed Web of Science ®Google Scholar
• Chavez AR, Buchser W, Basse PH, et al. Pharmacologic administration of interleukin-2. Ann NY Acad Sci 2009;1182:14-27
   PubMed Web of Science ®Google Scholar
• Rosenberg SA, Yang JC, White DE, Steinberg SM. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann Surg 1998;228(3):307-19
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Prieto PA, Yang JC, Sherry RM, et al. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res 2012;18(7):2039-47
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Weber JS, Maio M, et al. Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials. Ann Oncol 2013;24(8):2174-80
   PubMed Web of Science ®Google Scholar
• Lipson EJ, Sharfman WH, Drake CG, et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res 2013;19(2):462-8
   PubMed Web of Science ®Google Scholar
• Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366(26):2455-65
   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(26):2443-54
   PubMed Web of Science ®Google Scholar
• Schwartzentruber DJ, Lawson DH, Richards JM, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 2011;364(22):2119-27
   PubMed Web of Science ®Google Scholar
• Yang JC, Sherry RM, Steinberg SM, et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 2003;21(16):3127-32
   PubMed Web of Science ®Google Scholar
• Ohnishi H, Lin KM, Chu TM. Prolongation of serum half-life of interleukin 2 and augmentation of lymphokine-activated killer cell activity by pepstatin in mice. Cancer Res 1990;50(4):1107-12
   PubMed Web of Science ®Google Scholar
• Krieg C, Letourneau S, Pantaleo G, Boyman O. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci USA 2010;107(26):11906-11
   PubMed Web of Science ®Google Scholar
• Long SA, Rieck M, Sanda S, et al. Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs beta-cell function. Diabetes 2012;61(9):2340-8
   PubMed Web of Science ®Google Scholar
• Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med 2011;365(22):2055-66
   PubMed Web of Science ®Google Scholar
• Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med 2011;365(22):2067-77
   PubMed Web of Science ®Google Scholar
• Matsuoka K, Koreth J, Kim HT, et al. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. Sci Transl Med 2013;5(179):179ra143
   Web of Science ®Google Scholar
• Ahmadzadeh M, Rosenberg SA. IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood 2006;107(6):2409-14
   PubMed Web of Science ®Google Scholar
• Bluestone JA. The yin and yang of interleukin-2-mediated immunotherapy. N Engl J Med 2011;365(22):2129-31
   PubMed Web of Science ®Google Scholar
• Bonifacio E. Immunotherapy in type 1 diabetes: a shorter but more winding road? Diabetes 2012;61(9):2214-15
   PubMed Web of Science ®Google Scholar
• Melder RJ, Osborn BL, Riccobene T, et al. Pharmacokinetics and in vitro and in vivo anti-tumor response of an interleukin-2-human serum albumin fusion protein in mice. Cancer Immunol Immunother 2005;54(6):535-47
   PubMed Web of Science ®Google Scholar
• Osborn BL, Gu M, Grzegorzewski KJ, et al. Preliminary pharmacokinetic evaluation of Albuleukin; an interleukin-2 human serum albumin fusion protein, in solid tumor patients. AACR Meeting Abstracts 2004;45:4757
   Google Scholar
• Ricordi C, Strom TB. Clinical islet transplantation: advances and immunological challenges. Nat Rev Immunol 2004;4(4):259-68
   PubMed Web of Science ®Google Scholar
• Koulmanda M, Qipo A, Fan Z, et al. Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term triple therapy. Am J Transplant 2012;12(5):1296-302
   PubMed Web of Science ®Google Scholar
• Millington T, Koulmanda M, Ng C, et al. Effects of an agonist interleukin-2/Fc fusion protein, a mutant antagonist interleukin-15/Fc fusion protein, and sirolimus on cardiac allograft survival in non-human primates. J Heart Lung Transplant 2012;31(4):427-35
   PubMed Web of Science ®Google Scholar
• O'Malley BW Jr, Li D, McQuone SJ, Ralston R. Combination nonviral interleukin-2 gene immunotherapy for head and neck cancer: from bench top to bedside. Laryngoscope 2005;115(3):391-404
   PubMed Web of Science ®Google Scholar
• Hanes J, Sills A, Zhao Z, et al. Controlled local delivery of interleukin-2 by biodegradable polymers protects animals from experimental brain tumors and liver tumors. Pharm Res 2001;18(7):899-906
   PubMed Web of Science ®Google Scholar
• Egilmez NK, Jong YS, Sabel MS, et al. In situ tumor vaccination with interleukin-12-encapsulated biodegradable microspheres: induction of tumor regression and potent antitumor immunity. Cancer Res 2000;60(14):3832-7
   PubMed Web of Science ®Google Scholar
• Addison CL, Braciak T, Ralston R, et al. Intratumoral injection of an adenovirus expressing interleukin 2 induces regression and immunity in a murine breast cancer model. Proc Natl Acad Sci USA 1995;92(18):8522-6
   PubMed Web of Science ®Google Scholar
• Gansbacher B, Zier K, Daniels B, et al. Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 1990;172(4):1217-24
   PubMed Web of Science ®Google Scholar
• McAdam AJ, Pulaski BA, Harkins SS, et al. Synergistic effects of co-expression of the TH1 cytokines IL-2 and IFN-gamma on generation of murine tumor-reactive cytotoxic cells. Int J Cancer 1995;61(5):628-34
   PubMed Web of Science ®Google Scholar
• Gerber SA, Sorensen EW, Sedlacek AL, et al. Local expression of interleukin-2 by B16 melanoma cells results in decreased tumour growth and long-term tumour dormancy. Immunology 2013;138(3):280-92
   PubMed Web of Science ®Google Scholar
• Gajewski TF, Woo SR, Zha Y, et al. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol 2013;25(2):268-76
   PubMed Web of Science ®Google Scholar
• List T, Neri D. Immunocytokines: a review of molecules in clinical development for cancer therapy. Clin Pharmacol 2013;5:29-45
   PubMedGoogle Scholar
• Schrama D, Reisfeld RA, Becker JC. Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov 2006;5(2):147-59
   PubMed Web of Science ®Google Scholar
• Dela Cruz JS, Huang TH, Penichet ML, Morrison SL. Antibody-cytokine fusion proteins: innovative weapons in the war against cancer. Clin Exp Med 2004;4(2):57-64
   PubMed Web of Science ®Google Scholar
• Ribas A, Kirkwood JM, Atkins MB, et al. Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2) in patients with metastatic malignant melanoma. J Transl Med 2009;7:68
   PubMed Web of Science ®Google Scholar
• Delgado DC, Hank JA, Kolesar J, et al. Genotypes of NK cell KIR receptors, their ligands, and Fcgamma receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res 2010;70(23):9554-61
   PubMed Web of Science ®Google Scholar
• Koehn TA, Trimble LL, Alderson KL, et al. Increasing the clinical efficacy of NK and antibody-mediated cancer immunotherapy: potential predictors of successful clinical outcome based on observations in high-risk neuroblastoma. Front Pharmacol 2012;3:91
   PubMed Web of Science ®Google Scholar
• Neal ZC, Yang JC, Rakhmilevich AL, et al. Enhanced activity of hu14.18-IL2 immunocytokine against murine NXS2 neuroblastoma when combined with interleukin 2 therapy. Clin Cancer Res 2004;10(14):4839-47
   PubMed Web of Science ®Google Scholar
• Gubbels JA, Gadbaw B, Buhtoiarov IN, et al. Ab-IL2 fusion proteins mediate NK cell immune synapse formation by polarizing CD25 to the target cell-effector cell interface. Cancer Immunol Immunother 2011;60(12):1789-800
   PubMed Web of Science ®Google Scholar
• Lustgarten J, Marks J, Sherman LA. Redirecting effector T cells through their IL-2 receptors. J Immunol 1999;162(1):359-65
   PubMed Web of Science ®Google Scholar
• Yang RK, Kalogriopoulos NA, Rakhmilevich AL, et al. Intratumoral treatment of smaller mouse neuroblastoma tumors with a recombinant protein consisting of IL-2 linked to the Hu14.18 antibody increases intratumoral CD8+ T and NK cells and improves survival. Cancer Immunol Immunother 2013;62(8):1303-13
   PubMed Web of Science ®Google Scholar
• Yang RK, Kalogriopoulos NA, Rakhmilevich AL, et al. Intratumoral hu14.18-IL-2 (IC) induces local and systemic antitumor effects that involve both activated T and NK cells as well as enhanced IC retention. J Immunol 2012;189(5):2656-64
   PubMed Web of Science ®Google Scholar
• Gillies SD, Lan Y, Hettmann T, et al. A low-toxicity IL-2-based immunocytokine retains antitumor activity despite its high degree of IL-2 receptor selectivity. Clin Cancer Res 2011;17(11):3673-85
   PubMed Web of Science ®Google Scholar
• Shusterman S, London WB, Gillies SD, et al. Antitumor activity of hu14.18-IL2 in patients with relapsed/refractory neuroblastoma: a Children's Oncology Group (COG) phase II study. J Clin Oncol 2010;28(33):4969-75
   PubMed Web of Science ®Google Scholar
• Albertini MR, Hank JA, Gadbaw B, et al. Phase II trial of hu14.18-IL2 for patients with metastatic melanoma. Cancer Immunol Immunother 2012;61(12):2261-71
   PubMed Web of Science ®Google Scholar
• Finkelman FD, Madden KB, Morris SC, et al. Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes. J Immunol 1993;151(3):1235-44
   PubMed Web of Science ®Google Scholar
• Courtney LP, Phelps JL, Karavodin LM. An anti-IL-2 antibody increases serum half-life and improves anti-tumor efficacy of human recombinant interleukin-2. Immunopharmacology 1994;28(3):223-32
   PubMedGoogle Scholar
• Boyman O, Krieg C, Letourneau S, et al. Selectively expanding subsets of T cells in mice by injection of interleukin-2/antibody complexes: implications for transplantation tolerance. Transplant Proc 2012;44(4):1032-4
   PubMed Web of Science ®Google Scholar
• Boyman O, Kovar M, Rubinstein MP, et al. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 2006;311(5769):1924-7
   PubMed Web of Science ®Google Scholar
• Rojas G, Pupo A, Leon K, et al. Deciphering the molecular bases of the biological effects of antibodies against Interleukin-2: a versatile platform for fine epitope mapping. Immunobiology 2013;218(1):105-13
   PubMed Web of Science ®Google Scholar
• Kamimura D, Sawa Y, Sato M, et al. IL-2 in vivo activities and antitumor efficacy enhanced by an anti-IL-2 mAb. J Immunol 2006;177(1):306-14
   PubMed Web of Science ®Google Scholar
• Verdeil G, Marquardt K, Surh CD, Sherman LA. Adjuvants targeting innate and adaptive immunity synergize to enhance tumor immunotherapy. Proc Natl Acad Sci USA 2008;105(43):16683-8
   PubMed Web of Science ®Google Scholar
• Tomala J, Chmelova H, Mrkvan T, et al. In vivo expansion of activated naive CD8+ T cells and NK cells driven by complexes of IL-2 and anti-IL-2 monoclonal antibody as novel approach of cancer immunotherapy. J Immunol 2009;183(8):4904-12
   PubMed Web of Science ®Google Scholar
• Jin GH, Hirano T, Murakami M. Combination treatment with IL-2 and anti-IL-2 mAbs reduces tumor metastasis via NK cell activation. Int Immunol 2008;20(6):783-9
   PubMed Web of Science ®Google Scholar
• Rao BM, Girvin AT, Ciardelli T, et al. Interleukin-2 mutants with enhanced alpha-receptor subunit binding affinity. Protein Eng 2003;16(12):1081-7
   PubMedGoogle Scholar
• Rao BM, Driver I, Lauffenburger DA, Wittrup KD. High-affinity CD25-binding IL-2 mutants potently stimulate persistent T cell growth. Biochemistry 2005;44(31):10696-701
   PubMed Web of Science ®Google Scholar
• Rao BM, Driver I, Lauffenburger DA, Wittrup KD. Interleukin 2 (IL-2) variants engineered for increased IL-2 receptor alpha-subunit affinity exhibit increased potency arising from a cell surface ligand reservoir effect. Mol Pharmacol 2004;66(4):864-9
   PubMed Web of Science ®Google Scholar
• Shanafelt AB, Lin Y, Shanafelt MC, et al. A T-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo. Nat Biotechnol 2000;18(11):1197-202
   PubMed Web of Science ®Google Scholar
• Margolin K, Atkins MB, Dutcher JP, et al. Phase I trial of BAY 50-4798, an interleukin-2-specific agonist in advanced melanoma and renal cancer. Clin Cancer Res 2007;13(11):3312-19
   PubMed Web of Science ®Google Scholar
• Hulme MA, Wasserfall CH, Atkinson MA, Brusko TM. Central role for interleukin-2 in type 1 diabetes. Diabetes 2012;61(1):14-22
   PubMed Web of Science ®Google Scholar
• Ring AM, Lin JX, Feng D, et al. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat Immunol 2012;13(12):1187-95
   PubMed Web of Science ®Google Scholar
• Carmenate T, Pacios A, Enamorado M, et al. Human IL-2 Mutein with Higher Antitumor Efficacy Than Wild Type IL-2. J Immunol 2013;190(12):6230-8
   PubMed Web of Science ®Google Scholar
• Puskas J, Skrombolas D, Sedlacek A, et al. Development of an attenuated interleukin-2 fusion protein that can be activated by tumour-expressed proteases. Immunology 2011;133(2):206-20
   PubMed Web of Science ®Google Scholar
• Letourneau S, van Leeuwen EM, Krieg C, et al. IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25. Proc Natl Acad Sci USA 2010;107(5):2171-6
   PubMed Web of Science ®Google Scholar