IL-2/anti-IL-2 mAb immunocomplexes: A renascence of IL-2 in cancer immunotherapy?

OncoImmunology

Volumn 5, Issue 3, 2016, Pages

  Tomala, Jakub ^a   Kovar, Marek ^a  

^a INSTITUTE OF MICROBIOLOGY   (Czech Republic)

Author keywords

Anti IL 2 mAb; cancer immunotherapy; IL 2; immunocomplexes; selective stimulatory activity

Indexed keywords

ALPHA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HERMES ANTIGEN; INTERLEUKIN 2; INTERLEUKIN 2 MONOCLONAL ANTIBODY; INTERLEUKIN 2 RECEPTOR BETA; INTERLEUKIN 2 RECEPTOR GAMMA; INTERLEUKIN 3; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 6; INTERLEUKIN 7; L SELECTIN; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG;

ANTIGEN ANTIBODY COMPLEX; ANTINEOPLASTIC ACTIVITY; CANCER IMMUNOTHERAPY; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL PROLIFERATION; HOMEOSTASIS; HUMAN; KIDNEY CARCINOMA; NATURAL KILLER CELL; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REVIEW;

EID: 84961575875     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2015.1102829     Document Type: Review

References (84)

1. P.C.Nowell. Phytohemagglutinin: an initiator of mitosis in cultures of normal human leukocytes. Cancer Res 1960; 20:462-6; PMID:14427849
2. S.Kasakura, L.Lowenstein. A factor stimulating DNA synthesis derived from the medium of leukocyte cultures. Nature 1965; 208:794-5; PMID:5868897; http://dx.doi.org/10.1038/208794a0
3. J.Gordon, L.D.MacLean. A lymphocyte-stimulating factor produced in vitro. Nature 1965; 208:795-6; PMID:4223737; http://dx.doi.org/10.1038/208795a0
4. S.Gillis, K.A.Smith. Long term culture of tumour-specific cytotoxic T cells. Nature 1977; 268:154-6; PMID:145543; http://dx.doi.org/10.1038/268154a0
5. S.Gillis, M.M.Ferm, W.Ou, K.A.Smith. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol 1978; 120:2027-32; PMID:307029
6. I.Gery, R.K.Gershon, B.H.Waksman. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med 1972; 136:128-42; PMID:5033417; http://dx.doi.org/10.1084/jem.136.1.128
7. K.A.Smith, K.J.Gilbride, M.F.Favata. Lymphocyte activating factor promotes T-cell growth factor production by cloned murine lymphoma cells. Nature 1980; 287:853-5; PMID:6776414; http://dx.doi.org/10.1038/287853a0
8. K.A.Smith, L.B.Lachman, J.J.Oppenheim, M.F.Favata. The functional relationship of the interleukins. J Exp Med 1980; 151:1551-6; PMID:6770028; http://dx.doi.org/10.1084/jem.151.6.1551
9. K.A.Smith. Interleukin-2: inception, impact, and implications. Science 1988; 240:1169-76; PMID:3131876; http://dx.doi.org/10.1126/science.3131876
10. O.Boyman, J.Sprent. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 2012; 12:180-90; PMID:22343569; http://dx.doi.org/10.1126/science.1122927
11. S.Gillis. Interleukin 2: biology and biochemistry. J Clin Immunol 1983; 3:1-13; PMID:6338024; http://dx.doi.org/10.1007/BF00919133
12. R.B.Herberman. Natural killer cells. Annu Rev Med 1986; 37:347-52; PMID:3518610; http://dx.doi.org/10.1146/annurev.me.37.020186.002023
13. Y.S.Choi. Differentiation and apoptosis of human germinal center B-lymphocytes. Immunol Res 1997; 16:161-74; PMID:9212362; http://dx.doi.org/10.1007/BF02786360
14. M.H.Oppenheim, M.T.Lotze. Interleukin-2: solid-tumor therapy. Oncology 1994; 51:154-69; PMID:8196899; http://dx.doi.org/10.1159/000227330
15. K.Somersalo. Migratory functions of natural killer cells. Nat Immun 1996; 15:117-33; PMID:9162262
16. J.G.Johnson, M.K.Jenkins. Co-stimulatory functions of antigen-presenting cells. J Invest Dermatol 1992; 99:62S-5S; PMID:1358981; http://dx.doi.org/10.1111/1523-1747.ep12669010
17. E.V.Rothenberg, S.B.Ward. A dynamic assembly of diverse transcription factors integrates activation and cell-type information for interleukin 2 gene regulation. Proc Natl Acad Sci U S A 1996; 93:9358-65; PMID:8790334; http://dx.doi.org/10.1073/pnas.93.18.9358
18. R.H.Schwartz. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 1992; 71:1065-8; PMID:1335362; http://dx.doi.org/10.1016/S0092-8674(05)80055-8
19. D.J.Stauber, E.W.Debler, P.A.Horton, K.A.Smith, I.A.Wilson. Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci U S A 2006; 103:2788-93; PMID:16477002; http://dx.doi.org/10.1073/pnas.0511161103
20. H.M.Wang, K.A.Smith. The interleukin 2 receptor. Functional consequences of its bimolecular structure. J Exp Med 1987; 166:1055-69; PMID:3116143; http://dx.doi.org/10.1084/jem.166.4.1055
21. B.H.Nelson, D.M.Willerford. Biology of the interleukin-2 receptor. Adv Immunol 1998; 70:1-81; PMID:9755337; http://dx.doi.org/10.1016/S0065-2776(08)60386-7
22. X.Zhang, S.Sun, I.Hwang, D.F.Tough, J.Sprent. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 1998; 8:591-9; PMID:9620680; http://dx.doi.org/10.1016/S1074-7613(00)80564-6
23. M.Brisslert, M.Bokarewa, P.Larsson, K.Wing, L.V.Collins, A.Tarkowski. Phenotypic and functional characterization of human CD25+ B cells. Immunology 2006; 117:548-57; PMID:16556269; http://dx.doi.org/10.1111/j.1365-2567.2006.02331.x
24. I.Espinoza-Delgado, J.R.Ortaldo, R.Winkler-Pickett, K.Sugamura, L.Varesio, D.L.Longo. Expression and role of p75 interleukin 2 receptor on human monocytes. J Exp Med 1990; 171:1821-6; PMID:2110244; http://dx.doi.org/10.1084/jem.171.5.1821
25. V.Kronin, D.Vremec, K.Shortman. Does the IL-2 receptor alpha chain induced on dendritic cells have a biological function? Int Immunol 1998; 10:237-40; PMID:9533452; http://dx.doi.org/10.1093/intimm/10.2.237
26. S.Hodge, G.Hodge, R.Flower, P.Han. Surface and intracellular interleukin-2 receptor expression on various resting and activated populations involved in cell-mediated immunity in human peripheral blood. Scand J Immunol 2000; 51:67-72; PMID:10632978; http://dx.doi.org/10.1046/j.1365-3083.2000.00644.x
27. J.D.Fontenot, J.P.Rasmussen, M.A.Gavin, A.Y.Rudensky. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 2005; 6:1142-51; PMID:16227984; http://dx.doi.org/10.1038/ni1263
28. T.R.Malek, A.L.Bayer. Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 2004; 4:665-74; PMID:15343366; http://dx.doi.org/10.1038/nri1435
29. A.Comes, O.Rosso, A.M.Orengo, E.Di Carlo, C.Sorrentino, R.Meazza, T.Piazza, B.Valzasina, P.Nanni, M.P.Colombo et al. CD25+ regulatory T cell depletion augments immunotherapy of micrometastases by an IL-21-secreting cellular vaccine. J Immunol 2006; 176:1750-8; PMID:16424205; http://dx.doi.org/10.4049/jimmunol.176.3.1750
30. S.Suvas, U.Kumaraguru, C.D.Pack, S.Lee, B.T.Rouse. CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J Exp Med 2003; 198:889-901; PMID:12975455; http://dx.doi.org/10.1084/jem.20030171
31. K.Ko, S.Yamazaki, K.Nakamura, T.Nishioka, K.Hirota, T.Yamaguchi, J.Shimizu, T.Nomura, T.Chiba, S.Sakaguchi. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J Exp Med 2005; 202:885-91; PMID:16186187; http://dx.doi.org/10.1084/jem.20050940
32. S.Sakaguchi. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004; 22:531-62; PMID:15032588; http://dx.doi.org/10.1146/annurev.immunol.21.120601.141122
33. S.A.Rosenberg. IL-2: the first effective immunotherapy for human cancer. J Immunol 2014; 192:5451-8; PMID:24907378; http://dx.doi.org/10.4049/jimmunol.1490019
34. S.A.Rosenberg, M.T.Lotze, L.M.Muul, S.Leitman, A.E.Chang, S.E.Ettinghausen, Y.L.Matory, J.M.Skibber, E.Shiloni, J.T.Vetto et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 1985; 313:1485-92; PMID:3903508; http://dx.doi.org/10.1056/NEJM198512053132327
35. S.A.Rosenberg, M.T.Lotze, L.M.Muul, A.E.Chang, F.P.Avis, S.Leitman, W.M.Linehan, C.N.Robertson, R.E.Lee, J.T.Rubin et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 1987; 316:889-97; PMID:3493432; http://dx.doi.org/10.1056/NEJM198704093161501
36. S.A.Rosenberg, J.C.Yang, S.L.Topalian, D.J.Schwartzentruber, J.S.Weber, D.R.Parkinson, C.A.Seipp, J.H.Einhorn, D.E.White. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 1994; 271:907-13; PMID:8120958; http://dx.doi.org/10.1001/jama.1994.03510360033032
37. K.D.Griffith, E.J.Read, J.A.Carrasquillo, C.S.Carter, J.C.Yang, B.Fisher, P.Aebersold, B.S.Packard, M.Y.Yu, S.A.Rosenberg. In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma. J Natl Cancer Inst 1989; 81:1709-17; PMID:2810387; http://dx.doi.org/10.1093/jnci/81.22.1709
38. S.A.Rosenberg, J.R.Yannelli, J.C.Yang, S.L.Topalian, D.J.Schwartzentruber, J.S.Weber, D.R.Parkinson, C.A.Seipp, J.H.Einhorn, D.E.White. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 1994; 86:1159-66; PMID:8028037; http://dx.doi.org/10.1093/jnci/86.15.1159
39. S.A.Rosenberg, B.S.Packard, P.M.Aebersold, D.Solomon, S.L.Topalian, S.T.Toy, P.Simon, M.T.Lotze, J.C.Yang, C.A.Seipp et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 1988; 319:1676-80; PMID:3264384; http://dx.doi.org/10.1056/NEJM198812223192527
40. L.M.Muul, P.J.Spiess, E.P.Director, S.A.Rosenberg. Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol 1987; 138:989-95; PMID:3100623
41. M.E.Dudley, J.R.Wunderlich, P.F.Robbins, J.C.Yang, P.Hwu, D.J.Schwartzentruber, S.L.Topalian, R.Sherry, N.P.Restifo, A.M.Hubicki et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002; 298:850-4; PMID:12242449; http://dx.doi.org/10.1126/science.1076514
42. D.A.Cooper, S.Emery. Latent reservoirs of HIV infection: flushing with IL-2? Nat Med 1999; 5:611-2; PMID:10371491; http://dx.doi.org/10.1038/9454
43. I.Sereti, K.B.Anthony, H.Martinez-Wilson, R.Lempicki, J.Adelsberger, J.A.Metcalf, C.W.Hallahan, D.Follmann, R.T.Davey, J.A.Kovacs et al. IL-2-induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation. Blood 2004; 104:775-80; PMID:15090457; http://dx.doi.org/10.1182/blood-2003-12-4355
44. I.-E.S.Group, S.S.Committee, D.Abrams, Y.Levy, M.H.Losso, A.Babiker, G.Collins, D.A.Cooper, J.Darbyshire, S.Emery et al. Interleukin-2 therapy in patients with HIV infection. N Engl J Med 2009; 361:1548-59; PMID:19828532; http://dx.doi.org/10.1056/NEJMoa0903175
45. M.Liu, B.Acres, J.M.Balloul, N.Bizouarne, S.Paul, P.Slos, P.Squiban. Gene-based vaccines and immunotherapeutics. Proc Natl Acad Sci U S A 2004; 101 Suppl 2:14567-71; PMID:15333750; http://dx.doi.org/10.1073/pnas.0404845101
46. S.E.Parker, S.Khatibi, M.Margalith, D.Anderson, M.Yankauckas, S.H.Gromkowski, T.Latimer, D.Lew, M.Marquet, M.Manthorpe et al. Plasmid DNA gene therapy: studies with the human interleukin-2 gene in tumor cells in vitro and in the murine B16 melanoma model in vivo. Cancer Gene Ther 1996; 3:175-85; PMID:8725882
47. R.J.Melder, B.L.Osborn, T.Riccobene, P.Kanakaraj, P.Wei, G.Chen, D.Stolow, W.G.Halpern, T.S.Migone, Q.Wang 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; 54:535-47; PMID:15592670; http://dx.doi.org/10.1007/s00262-004-0624-7
48. A.Klimka, N.Yu, E.Y.Shami. Construction of proteolysis resistant human interleukin-2 by fusion to its protective single chain antibody. Cytokine 2003; 22:134-41; PMID:12842761; http://dx.doi.org/10.1016/S1043-4666(03)00136-4
49. D.H.Barouch, D.M.Truitt, N.L.Letvin. Expression kinetics of the interleukin-2/immunoglobulin (IL-2/Ig) plasmid cytokine adjuvant. Vaccine 2004; 22:3092-7; PMID:15297060; http://dx.doi.org/10.1016/j.vaccine.2004.01.065
50. N.V.Katre, M.J.Knauf, W.J.Laird. Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model. Proc Natl Acad Sci U S A 1987; 84:1487-91; PMID:3494243; http://dx.doi.org/10.1073/pnas.84.6.1487
51. O.Boyman, M.Kovar, M.P.Rubinstein, C.D.Surh, J.Sprent. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 2006; 311:1924-7; PMID:16484453; http://dx.doi.org/10.1126/science.1122927
52. C.C.Ku, M.Murakami, A.Sakamoto, J.Kappler, P.Marrack. Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 2000; 288:675-8; PMID:10784451; http://dx.doi.org/10.1126/science.288.5466.675
53. M.Murakami, A.Sakamoto, J.Bender, J.Kappler, P.Marrack. CD25+CD4+ T cells contribute to the control of memory CD8+ T cells. Proc Natl Acad Sci U S A 2002; 99:8832-7; PMID:12084927; http://dx.doi.org/10.1073/pnas.132254399
54. D.Kamimura, N.Ueda, Y.Sawa, S.Hachida, T.Atsumi, T.Nakagawa, S.Sawa, G.H.Jin, H.Suzuki, K.Ishihara et al. Evidence of a novel IL-2/15R β-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells. J Immunol 2004; 173:6041-9; PMID:15528339; http://dx.doi.org/10.4049/jimmunol.173.10.6041
55. J.Tomala, H.Chmelova, T.Mrkvan, B.Rihova, M.Kovar. 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; 183:4904-12; PMID:19801515; http://dx.doi.org/10.4049/jimmunol.0900284
56. K.E.Webster, S.Walters, R.E.Kohler, T.Mrkvan, O.Boyman, C.D.Surh, S.T.Grey, J.Sprent. In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J Exp Med 2009; 206:751-60; PMID:19332874; http://dx.doi.org/10.1084/jem.20082824
57. F.D.Finkelman, K.B.Madden, S.C.Morris, J.M.Holmes, N.Boiani, I.M.Katona, C.R.Maliszewski. 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; 151:1235-44; PMID:8393043
58. A.T.Jones, H.J.Ziltener. Enhancement of the biologic effects of interleukin-3 in vivo by anti-interleukin-3 antibodies. Blood 1993; 82:1133-41; PMID:8353280
59. H.Heremans, C.Dillen, W.Put, J.Van Damme, A.Billiau. Protective effect of anti-interleukin (IL)-6 antibody against endotoxin, associated with paradoxically increased IL-6 levels. Eur J Immunol 1992; 22:2395-401; PMID:1381315; http://dx.doi.org/10.1002/eji.1830220932
60. E.Martens, C.Dillen, W.Put, H.Heremans, J.van Damme, A.Billiau. Increased circulating interleukin-6 (IL-6) activity in endotoxin-challenged mice pretreated with anti-IL-6 antibody is due to IL-6 accumulated in antigen-antibody complexes. Eur J Immunol 1993; 23:2026-9; PMID:8344369; http://dx.doi.org/10.1002/eji.1830230846
61. O.Boyman, C.Ramsey, D.M.Kim, J.Sprent, C.D.Surh. IL-7/anti-IL-7 mAb complexes restore T cell development and induce homeostatic T Cell expansion without lymphopenia. J Immunol 2008; 180:7265-75; PMID:18490726; http://dx.doi.org/10.4049/jimmunol.180.11.7265
62. M.P.Rubinstein, M.L.Salem, A.L.Doedens, C.J.Moore, C.Chiuzan, G.L.Rivell, D.J.Cole, A.W.Goldrath. G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b+Gr-1+ myeloid cells without compromising CD8+ T cell immune responses. J Hematol Oncol 2013; 6:75; PMID:24279871; http://dx.doi.org/10.1186/1756-8722-6-75
63. L.Zabeau, J.Van der Heyden, D.Broekaert, A.Verhee, J.Vandekerckhove, S.J.Wu, I.Chaiken, P.Heinrich, I.Behrmann, J.Tavernier. Neutralizing monoclonal antibodies can potentiate IL-5 signaling. Eur J Immunol 2001; 31:1087-97; PMID:11298333; http://dx.doi.org/10.1002/1521-4141(200104)31:4%3c1087::AID-IMMU1087%3e3.0.CO;2-Q
64. M.G.Rosenblum, B.W.Unger, J.U.Gutterman, E.M.Hersh, G.S.David, J.M.Frincke. Modification of human leukocyte interferon pharmacology with a monoclonal antibody. Cancer Res 1985; 45:2421-4; PMID:3986783
65. S.E.Hamilton, J.M.Schenkel, A.D.Akue, S.C.Jameson. IL-2 complex treatment can protect naive mice from bacterial and viral infection. J Immunol 2010; 185:6584-90; PMID:21037095; http://dx.doi.org/10.4049/jimmunol.1001215
66. D.Kamimura, Y.Sawa, M.Sato, E.Agung, T.Hirano, M.Murakami. IL-2 in vivo activities and antitumor efficacy enhanced by an anti-IL-2 mAb. J Immunol 2006; 177:306-14; PMID:16785526; http://dx.doi.org/10.4049/jimmunol.177.1.306
67. G.Rojas, Y.Cabrera Infante, A.Pupo, T.Carmenate. Fine epitope specificity of antibodies against interleukin-2 explains their paradoxical immunomodulatory effects. MAbs 2014; 6:273-85; PMID:24253188; http://dx.doi.org/10.4161/mabs.27224
68. J.Tomala, H.Chmelova, J.Strohalm, K.Ulbrich, M.Sirova, B.Rihova, M.Kovar. Antitumor activity of IL-2/anti-IL-2 mAb immunocomplexes exerts synergism with that of N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugate due to its low immunosuppressive activity. Int J Cancer 2011; 129:2002-12; PMID:21165950; http://dx.doi.org/10.1002/ijc.25859
69. R.Liu, Q.Zhou, A.La Cava, D.I.Campagnolo, L.Van Kaer, F.D.Shi. Expansion of regulatory T cells via IL-2/anti-IL-2 mAb complexes suppresses experimental myasthenia. Eur J Immunol 2010; 40:1577-89; PMID:20352624; http://dx.doi.org/10.1002/eji.200939792
70. D.Kamimura, M.J.Bevan. Naive CD8+ T cells differentiate into protective memory-like cells after IL-2 anti IL-2 complex treatment in vivo. J Exp Med 2007; 204:1803-12; PMID:17664293; http://dx.doi.org/10.1084/jem.20070543
71. G.Verdeil, K.Marquardt, C.D.Surh, L.A.Sherman. Adjuvants targeting innate and adaptive immunity synergize to enhance tumor immunotherapy. Proc Natl Acad Sci U S A 2008; 105:16683-8; PMID:18936481; http://dx.doi.org/10.1073/pnas.0805054105
72. D.J.Schwartzentruber. Biologic therapy with interleukin-2: clinical applications. Principles of administration and management of side effects. Philadelphia:Lippincott Williams & Wilkins, 1995.
73. R.N.Schwartz, L.Stover, J.Dutcher. Managing toxicities of high-dose interleukin-2. Oncology (Williston Park) 2002; 16:11-20; PMID:12469935
74. W.H.West, K.W.Tauer, J.R.Yannelli, G.D.Marshall, D.W.Orr, G.B.Thurman, R.K.Oldham. Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med 1987; 316:898-905; PMID:3493433; http://dx.doi.org/10.1056/NEJM198704093161502
75. C.Krieg, S.Letourneau, G.Pantaleo, O.Boyman. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci U S A 2010; 107:11906-11; PMID:20547866; http://dx.doi.org/10.1073/pnas.1002569107
76. A.L.Epstein, M.M.Mizokami, J.Li, P.Hu, L.A.Khawli. Identification of a protein fragment of interleukin 2 responsible for vasopermeability. J Natl Cancer Inst 2003; 95:741-9; PMID:12759392; http://dx.doi.org/10.1093/jnci/95.10.741
77. S.Letourneau, E.M.van Leeuwen, C.Krieg, C.Martin, G.Pantaleo, J.Sprent, C.D.Surh, O.Boyman. 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 U S A 2010; 107:2171-6; PMID:20133862; http://dx.doi.org/10.1073/pnas.0909384107
78. J.D.Phelan, T.Orekov, F.D.Finkelman. Cutting edge: mechanism of enhancement of in vivo cytokine effects by anti-cytokine monoclonal antibodies. J Immunol 2008; 180:44-8; PMID:18097002; http://dx.doi.org/10.4049/jimmunol.180.1.44
79. G.Rojas, A.Pupo, K.Leon, J.Avellanet, T.Carmenate, S.Sidhu. Deciphering the molecular bases of the biological effects of antibodies against Interleukin-2: a versatile platform for fine epitope mapping. Immunobiology 2013; 218:105-13; PMID:22459271; http://dx.doi.org/10.1016/j.imbio.2012.02.009
80. J.Tomala, J.Kovarova, M.Kabesova, P.Votavova, H.Chmelova, B.Dvorakova, B.Rihova, M.Kovar. Chimera of IL-2 linked to light chain of anti-IL-2 mAb mimics IL-2/anti-IL-2 mAb complexes both structurally and functionally. ACS Chem Biol 2013; 8:871-6; PMID:23419043; http://dx.doi.org/10.1021/cb3007242
81. J.B.Spangler, J.Tomala, V.C.Luca, K.M.Jude, S.Dong, A.M.Ring, P.Votavova, M.Pepper, M.Kovar, K.C.Garcia. Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms. Immunity 2015; 42:815-25; PMID:25992858; http://dx.doi.org/10.1016/j.immuni.2015.04.015
82. T.Carmenate, A.Pacios, M.Enamorado, E.Moreno, K.Garcia-Martinez, D.Fuente, K.León. Human IL-2 mutein with higher antitumor efficacy than wild type IL-2. J Immunol 2013; 190:6230-8; PMID:23677467; http://dx.doi.org/10.4049/jimmunol.1201895
83. A.M.Levin, D.L.Bates, A.M.Ring, C.Krieg, J.T.Lin, L.Su, I.Moraga, M.E.Raeber, G.R.Bowman, P.Novick et al. Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’. Nature 2012; 484:529-33; PMID:22446627; http://dx.doi.org/10.1038/nature10975
84. M.J.Molloy, W.Zhang, E.J.Usherwood. Cutting edge: IL-2 immune complexes as a therapy for persistent virus infection. J Immunol 2009; 182:4512-5; PMID:19342623; http://dx.doi.org/10.4049/jimmunol.0804175