IL-15 superagonist/IL-15RαSushi-Fc fusion complex (IL-15SA/IL-15RαSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity against murine breast and colon carcinomas

Oncotarget

Volumn 7, Issue 13, 2016, Pages 16130-16145

  Kim, Peter S ^a   Kwilas, Anna R ^a   Xu, Wenxin ^b   Alter, Sarah ^b   Jeng, Emily K ^b   Wong, Hing C ^b   Schlom, Jeffrey ^a   Hodge, James W ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b ALTOR BIOSCIENCE CORPORATION   (United States)

Author keywords

IL 15; IL 15 superagonist; Immunotherapy; NK cells

Indexed keywords

ANTIBODY; ANTINEOPLASTIC AGENT; CD11B ANTIGEN; CD27 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; HERMES ANTIGEN; INTERLEUKIN 15; INTERLEUKIN 15 SUPERAGONIST INTERLEUKIN 15 RECEPTOR ALPHA SUSHI FC FUSION PROTEIN; INTERLEUKIN 2 RECEPTOR BETA; NATURAL KILLER CELL RECEPTOR NKG2D; PROGRAMMED DEATH 1 LIGAND 1 ANTIBODY; PROGRAMMED DEATH 1 RECEPTOR; RECOMBINANT INTERLEUKIN 15; UNCLASSIFIED DRUG; ALT-803; PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CARCINOMA; CANCER SURVIVAL; CD8+ T LYMPHOCYTE; CELL EXPANSION; COLON CARCINOMA; CONTROLLED STUDY; DRUG POTENTIATION; FEMALE; IMMUNOMODULATION; LUNG METASTASIS; LYMPHOCYTE SUBPOPULATION; MEMORY T LYMPHOCYTE; MOUSE; NATURAL KILLER CELL; NONHUMAN; ANIMAL; BAGG ALBINO MOUSE; BREAST TUMOR; CARCINOMA; COLON TUMOR; DRUG EFFECTS; IMMUNOLOGICAL MEMORY; IMMUNOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CARCINOMA; CD8-POSITIVE T-LYMPHOCYTES; COLONIC NEOPLASMS; FEMALE; IMMUNOLOGIC MEMORY; KILLER CELLS, NATURAL; MICE; MICE, INBRED BALB C; PROTEINS;

EID: 84971667832     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.7470     Document Type: Article

References (50)

1. Tagaya Y, Bamford RN, DeFilippis AP, Waldmann TA. IL-15: a pleiotropic cytokine with diverse receptor/signaling pathways whose expression is controlled at multiple levels. Immunity. 1996; 4:329-336.
2. Ma A, Boone DL, Lodolce JP. The pleiotropic functions of interleukin 15: not so interleukin 2-like after all. J Exp Med. 2000; 191:753-756.
3. + Treg cells fit. Nat Immunol. 2005; 6:1071-1072.
4. Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol. 2005; 6:1142-1151.
5. D'Cruz LM, Klein L. Development and function of agonist-induced CD25+ Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol. 2005; 6:1152-1159.
6. Marks-Konczalik J, Dubois S, Losi JM, Sabzevari H, Yamada N, Feigenbaum L, Waldmann TA, Tagaya Y. IL-2-induced activationinduced cell death is inhibited in IL-15 transgenic mice. Proc Natl Acad Sci U S A. 2000; 97:11445-11450.
7. Waldmann TA. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nature reviews Immunology. 2006; 6:595-601.
8. Conlon KC, Lugli E, Welles HC, Rosenberg SA, Fojo AT, Morris JC, Fleisher TA, Dubois SP, Perera LP, Stewart DM, Goldman CK, Bryant BR, Decker JM, Chen J, Worthy TA, Figg WDS, et al. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol. 2015; 33:74-82.
9. Kobayashi H, Carrasquillo JA, Paik CH, Waldmann TA, Tagaya Y. Differences of biodistribution, pharmacokinetics, and tumor targeting between interleukins 2 and 15. Cancer Research. 2000; 60:3577-3583.
10. Zamai L, Ponti C, Mirandola P, Gobbi G, Papa S, Galeotti L, Cocco L, Vitale M. NK cells and cancer. J Immunol. 2007; 178:4011-4016.
11. Han KP, Zhu X, Liu B, Jeng E, Kong L, Yovandich JL, Vyas VV, Marcus WD, Chavaillaz PA, Romero CA, Rhode PR, Wong HC. IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine. 2011; 56:804-810.
12. Rubinstein MP, Kovar M, Purton JF, Cho JH, Boyman O, Surh CD, Sprent J. Converting IL-15 to a superagonist by binding to soluble IL-15R(alpha). Proc Natl Acad Sci U S A. 2006; 103:9166-9171.
13. Stoklasek TA, Schluns KS, Lefrancois L. Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol. 2006; 177:6072-6080.
14. + T cells into innate-like effector cells with antitumor activity. Oncoimmunology. 2013; 2:e26442.
15. Rhode PR, Egan JO, Xu W, Hong H, Webb GM, Chen X, Liu B, Zhu X, Wen J, You L, Kong L, Edwards AC, Han K, Shi S, Alter S, Sacha JB, et al. Comparison of the Superagonist Complex, ALT-803, to IL15 as Cancer Immunotherapeutics in Animal Models. Cancer Immunol Res. 2016; 4:49-60.
16. Xu W, Jones M, Liu B, Zhu X, Johnson CB, Edwards AC, Kong L, Jeng EK, Han K, Marcus WD, Rubinstein MP, Rhode PR, Wong HC. Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor alphaSu/Fc fusion complex in syngeneic murine models of multiple myeloma. Cancer Res. 2013; 73:3075-3086.
17. Gomes-Giacoia E, Miyake M, Goodison S, Sriharan A, Zhang G, You L, Egan JO, Rhode PR, Parker AS, Chai KX, Wong HC, Rosser CJ. Intravesical ALT-803 and BCG treatment reduces tumor burden in a carcinogen induced bladder cancer rat model; a role for cytokine production and NK cell expansion. PloS one. 2014; 9:e96705.
18. Mathios D, Park CK, Marcus WD, Alter S, Rhode PR, Jeng EK, Wong HC, Pardoll DM, Lim M. Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model. Int J Cancer. 2016; 138:187-194.
19. Leclercq G, Debacker V, de Smedt M, Plum J. Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells. J Exp Med. 1996; 184:325-336.
20. Hayakawa Y AD, Smyth MJ. Subset analysis of human and mouse mature NK cells. Methods Mol Biol 2010; 612:27-38.
21. Hayakawa Y, Huntington ND, Nutt SL, Smyth MJ. Functional subsets of mouse natural killer cells. Immunological reviews. 2006; 214:47-55.
22. Hayakawa Y, Smyth MJ. CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. J Immunol. 2006; 176:1517-1524.
23. Huntington ND, Tabarias H, Fairfax K, Brady J, Hayakawa Y, Degli-Esposti MA, Smyth MJ, Tarlinton DM, Nutt SL. NK cell maturation and peripheral homeostasis is associated with KLRG1 up-regulation. J Immunol. 2007; 178:4764-4770.
24. Ardiani A, Gameiro SR, Palena C, Hamilton DH, Kwilas A, King TH, Schlom J, Hodge JW. Vaccine-mediated immunotherapy directed against a transcription factor driving the metastatic process. Cancer Res. 2014; 74:1945-1957.
25. Pulaski BA, Ostrand-Rosenberg S. Mouse 4T1 breast tumor model. Current protocols in immunology / edited by John E Coligan [et al]. 2001; Chapter 20:Unit 20 22.
26. Seay K, Church C, Zheng JH, Deneroff K, Ochsenbauer C, Kappes JC, Liu B, Jeng EK, Wong HC, Goldstein H. In Vivo Activation of Human NK Cells by Treatment with an Interleukin-15 Superagonist Potently Inhibits Acute In Vivo HIV-1 Infection in Humanized Mice. Journal of virology. 2015; 89:6264-6274.
27. Ruocco MG, Pilones KA, Kawashima N, Cammer M, Huang J, Babb JS, Liu M, Formenti SC, Dustin ML, Demaria S. Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects. The Journal of clinical investigation. 2012; 122:3718-3730.
28. Sagiv-Barfi I, Kohrt HE, Czerwinski DK, Ng PP, Chang BY, Levy R. Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK. Proc Natl Acad Sci U S A. 2015; 112:E966-972.
29. Tirapu I, Huarte E, Guiducci C, Arina A, Zaratiegui M, Murillo O, Gonzalez A, Berasain C, Berraondo P, Fortes P, Prieto J, Colombo MP, Chen L, Melero I. Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma. Cancer Res. 2006; 66:2442-2450.
30. Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, Borquez-Ojeda O, Qu J, Wasielewska T, He Q, Bernal Y, Rijo IV, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Science translational medicine. 2013; 5:177ra138.
31. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. The New England journal of medicine. 2013; 368:1509-1518.
32. + T cells to compete for the memory cell niche. J Immunol. 2010; 185:4988-4992.
33. + T central-memory cell survival but not T effector-memory cell development. J Immunol. 2011; 187:5170-5182.
34. + T cells. Proc Natl Acad Sci U S A. 2006; 103:12075-12080.
35. + T cell fate coupled by T-bet and eomesodermin. Nat Immunol. 2005; 6:1236-1244.
36. + T cells increase antibacterial and anti-tumor immune responses: implications for immune function in aged mice. Journal of leukocyte biology. 2008; 84:1047-1056.
37. + T cells. Virology. 2005; 331:338-348.
38. Lanier LL. NK cell recognition. Annu rev Immunol. 2005; 23:225-274.
39. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008; 9:503-510.
40. Horowitz A, Strauss-Albee DM, Leipold M, Kubo J, Nemat-Gorgani N, Dogan OC, Dekker CL, Mackey S, Maecker H, Swan GE, Davis MM, Norman PJ, Guethlein LA, Desai M, Parham P, Blish CA. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Science translational medicine. 2013; 5:208ra145.
41. Keener AB. Natural killers: cataloging immune cells for immunotherapy. Nat Med. 2015; 21:207-208.
42. Leavy O. Natural killer cells: a virtual pick and mix. Nat Rev Immunol. 2013; 13:844-845.
43. Perez-Gracia JL, Labiano S, Rodriguez-Ruiz ME, Sanmamed MF, Melero I. Orchestrating immune check-point blockade for cancer immunotherapy in combinations. Current opinion in immunology. 2014; 27:89-97.
44. Kim PS, Ahmed R. Features of responding T cells in cancer and chronic infection. Current opinion in immunology. 2010; 22:223-230.
45. Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014; 515:563-567.
46. Mahoney KM, Atkins MB. Prognostic and predictive markers for the new immunotherapies. Oncology (Williston Park). 2014; 3:39-48.
47. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. The New England journal of medicine. 2012; 366:2443-2454.
48. Stojanovic A, Fiegler N, Brunner-Weinzierl M, Cerwenka A. CTLA-4 is expressed by activated mouse NK cells and inhibits NK Cell IFN-gamma production in response to mature dendritic cells. J Immunol. 2014; 192:4184-4191.
49. Wunderlich J, Shearer G. (1994). Induction and measurement of cytotoxic T lymphocyte activity. In: Coligan J, Kruisbeek A, Margulies D, Shevach E, Strober W, eds. Current Protocols in Immunology. (Hoboken, NJ: John Wiley and Sons), pp. 3.11.11.
50. Habu S, Fukui H, Shimamura K, Kasai M, Nagai Y, Okumura K, Tamaoki N. In vivo effects of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol. 1981; 127:34-38.