IL-15 receptor alpha as the magic wand to boost the success of IL-15 antitumor therapies: The upswing of IL-15 transpresentation

Pharmacology and Therapeutics

Volumn 170, Issue , 2017, Pages 73-79

  Van den Bergh, Johan MJ ^a   Lion, Eva ^a,b   Van Tendeloo, Viggo FI ^a   Smits, Evelien LJM ^a,b  

^a UNIVERSITY OF ANTWERP   (Belgium)

^b ANTWERP UNIVERSITY HOSPITAL   (Belgium)

Author keywords

Antitumor immunotherapies; Combination therapies; IL 15 receptor alpha; IL 15 transpresentation; Interleukin 15

Indexed keywords

INTERLEUKIN 15; INTERLEUKIN 15 RECEPTOR ALPHA; ANTINEOPLASTIC AGENT;

ANTINEOPLASTIC ACTIVITY; CANCER GENE THERAPY; CANCER IMMUNOTHERAPY; DRUG EFFICACY; DRUG SAFETY; HUMAN; NONHUMAN; PRECLINICAL STUDY; PRIORITY JOURNAL; REVIEW; ANIMAL; CD8+ T LYMPHOCYTE; HEMATOLOGIC NEOPLASMS; IMMUNOLOGY; NATURAL KILLER CELL; NEOPLASMS; PATHOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; CD8-POSITIVE T-LYMPHOCYTES; HEMATOLOGIC NEOPLASMS; HUMANS; INTERLEUKIN-15; INTERLEUKIN-15 RECEPTOR ALPHA SUBUNIT; KILLER CELLS, NATURAL; NEOPLASMS;

EID: 85005801903     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2016.10.012     Document Type: Review

References (59)

1. Anderson, D.M., Kumaki, S., Ahdieh, M., Bertles, J., Tometsko, M., Loomis, A., et al. Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes. J Biol Chem 270 (1995), 29862–29869.
2. Badoual, C., Bouchaud, G., Agueznay Nel, H., Mortier, E., Hans, S., Gey, A., et al. The soluble alpha chain of interleukin-15 receptor: a proinflammatory molecule associated with tumor progression in head and neck cancer. Cancer Res 68 (2008), 3907–3914.
3. Bergamaschi, C., Rosati, M., Jalah, R., Valentin, A., Kulkarni, V., Alicea, C., et al. Intracellular interaction of interleukin-15 with its receptor alpha during production leads to mutual stabilization and increased bioactivity. J Biol Chem 283 (2008), 4189–4199.
4. Chang, C.M., Lo, C.H., Shih, Y.M., Chen, Y., Wu, P.Y., Tsuneyama, K., et al. Treatment of hepatocellular carcinoma with adeno-associated virus encoding interleukin-15 superagonist. Hum Gene Ther 21 (2010), 611–621.
5. Cheever, M.A., Twelve immunotherapy drugs that could cure cancers. Immunol Rev 222 (2008), 357–368.
6. Cheng, L., Du, X., Su, L., Wang, S., Immunotherapy of metastatic and autochthonous liver cancer with IL-15/IL-15Ralpha fusion protein. Oncoimmunology, 3, 2014, e963409.
7. Chertova, E., Bergamaschi, C., Chertov, O., Sowder, R., Bear, J., Roser, J.D., et al. Characterization and favorable in vivo properties of heterodimeric soluble IL-15.IL-15Ralpha cytokine compared to IL-15 monomer. J Biol Chem 288 (2013), 18093–18103.
8. Cosman, D., Kumaki, S., Ahdieh, M., Eisenman, J., Grabstein, K.H., Paxton, R., et al. Interleukin 15 and its receptor. Ciba Found Symp 195 (1995), 221–229 (discussion 229-233).
9. Delconte, R.B., Kolesnik, T.B., Dagley, L.F., Rautela, J., Shi, W., Putz, E.M., et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat Immunol 17 (2016), 816–824.
10. Dubois, S., Mariner, J., Waldmann, T.A., Tagaya, Y., IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells. Immunity 17 (2002), 537–547.
11. Dubois, S., Patel, H.J., Zhang, M., Waldmann, T.A., Muller, J.R., 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 180 (2008), 2099–2106.
12. Elpek, K.G., Rubinstein, M.P., Bellemare-Pelletier, A., Goldrath, A.W., Turley, S.J., Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes. Proc Natl Acad Sci U S A 107 (2010), 21647–21652.
13. Epardaud, M., Elpek, K.G., Rubinstein, M.P., Yonekura, A.R., 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 68 (2008), 2972–2983.
14. Gaston, D.C., Odom, C.I., Li, L., Markert, J.M., Roth, J.C., Cassady, K.A., et al. Production of bioactive soluble interleukin-15 in complex with interleukin-15 receptor alpha from a conditionally-replicating oncolytic HSV-1. PLoS One, 8, 2013, e81768.
15. Giri, J.G., Ahdieh, M., Eisenman, J., Shanebeck, K., Grabstein, K., Kumaki, S., et al. Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J 13 (1994), 2822–2830.
16. Giron-Michel, J., Giuliani, M., Fogli, M., Brouty-Boye, D., Ferrini, S., Baychelier, F., et al. Membrane-bound and soluble IL-15/IL-15Ralpha complexes display differential signaling and functions on human hematopoietic progenitors. Blood 106 (2005), 2302–2310.
17. Gomes-Giacoia, E., Miyake, M., Goodison, S., Sriharan, A., Zhang, G., You, L., et al. 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, 9, 2014, e96705.
18. Grabstein, K.H., Eisenman, J., Shanebeck, K., Rauch, C., Srinivasan, S., Fung, V., et al. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 264 (1994), 965–968.
19. Guo, Y., Luan, L., Rabacal, W., Bohannon, J.K., Fensterheim, B.A., Hernandez, A., et al. IL-15 superagonist-mediated immunotoxicity: role of NK cells and IFN-gamma. J Immunol 195 (2015), 2353–2364.
20. Han, K.P., Zhu, X., Liu, B., Jeng, E., Kong, L., Yovandich, J.L., et al. IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine 56 (2011), 804–810.
21. Hong, E., Usiskin, I.M., Bergamaschi, C., Hanlon, D.J., Edelson, R.L., Justesen, S., et al. Configuration-dependent presentation of multivalent IL-15:IL-15Ralpha enhances the antigen-specific T cell response and anti-tumor immunity. J Biol Chem 291 (2016), 8931–8950.
22. Huntington, N.D., Legrand, N., Alves, N.L., Jaron, B., Weijer, K., Plet, A., et al. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med 206 (2009), 25–34.
23. Kermer, V., Hornig, N., Harder, M., Bondarieva, A., Kontermann, R.E., Muller, D., Combining antibody-directed presentation of IL-15 and 4-1BBL in a trifunctional fusion protein for cancer immunotherapy. Mol Cancer Ther 13 (2014), 112–121.
24. Khawam, K., Giron-Michel, J., Gu, Y., Perier, A., Giuliani, M., Caignard, A., et al. Human renal cancer cells express a novel membrane-bound interleukin-15 that induces, in response to the soluble interleukin-15 receptor alpha chain, epithelial-to-mesenchymal transition. Cancer Res 69 (2009), 1561–1569.
25. Kim, P.S., Kwilas, A.R., Xu, W., Alter, S., Jeng, E.K., Wong, H.C., et al. IL-15 superagonist/IL-15RalphaSushi-Fc fusion complex (IL-15SA/IL-15RalphaSu-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, 2016.
26. Kobayashi, H., Dubois, S., Sato, N., Sabzevari, H., Sakai, Y., Waldmann, T.A., et al. Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 105 (2005), 721–727.
27. Kokaji, A.I., Hockley, D.L., Kane, K.P., IL-15 transpresentation augments CD8 + T cell activation and is required for optimal recall responses by central memory CD8 + T cells. J Immunol 180 (2008), 4391–4401.
28. Liu, B., Kong, L., Han, K., Hong, H., Marcus, W.D., Chen, X., et al. A novel fusion of ALT-803 (IL-15 superagonist) with an antibody demonstrates antigen-specific antitumor responses. J Biol Chem, 2016.
29. Mathios, D., Park, C.K., Marcus, W.D., Alter, S., Rhode, P.R., Jeng, E.K., et al. 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 138 (2016), 187–194.
30. Morris, J.C., Ramlogan-Steel, C.A., Yu, P., Black, B.A., Mannan, P., Allison, J.P., et al. Vaccination with tumor cells expressing IL-15 and IL-15Ralpha inhibits murine breast and prostate cancer. Gene Ther 21 (2014), 393–401.
31. Mortier, E., Quemener, A., Vusio, P., Lorenzen, I., Boublik, Y., Grotzinger, J., et al. Soluble interleukin-15 receptor alpha (IL-15R alpha)-sushi as a selective and potent agonist of IL-15 action through IL-15R beta/gamma. Hyperagonist IL-15 × IL-15R alpha fusion proteins. J Biol Chem 281 (2006), 1612–1619.
32. Mortier, E., Woo, T., Advincula, R., Gozalo, S., Ma, A., IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med 205 (2008), 1213–1225.
33. Muller, D., Targeted cancer immunotherapy: mimicking physiological trans-presentation of IL-15. Oncoimmunology 1 (2012), 1213–1214.
34. Ochoa, M.C., Fioravanti, J., Rodriguez, I., Hervas-Stubbs, S., Azpilikueta, A., Mazzolini, G., et al. Antitumor immunotherapeutic and toxic properties of an HDL-conjugated chimeric IL-15 fusion protein. Cancer Res 73 (2013), 139–149.
35. Ota, N., Takase, M., Uchiyama, H., Olsen, S.K., Kanagawa, O., No requirement of trans presentations of IL-15 for human CD8 T cell proliferation. J Immunol 185 (2010), 6041–6048.
36. Polansky, J.K., Bahri, R., Divivier, M., Duitman, E.H., Vock, C., Goyeneche-Patino, D.A., et al. High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner. Sci Rep, 6, 2016, 19699.
37. Rhode, P.R., Egan, J.O., Xu, W., Hong, H., Webb, G.M., Chen, X., et al. Comparison of the superagonist complex, ALT-803, to IL15 as cancer immunotherapeutics in animal models. Cancer Immunol Res 4 (2016), 49–60.
38. Rosario, M., Liu, B., Kong, L., Collins, L.I., Schneider, S.E., Chen, X., et al. The IL-15-based ALT-803 complex enhances FcgammaRIIIa-triggered NK cell responses and in vivo clearance of B cell lymphomas. Clin Cancer Res 22 (2016), 596–608.
39. Rowley, J., Monie, A., Hung, C.F., Wu, T.C., Inhibition of tumor growth by NK1.1 + cells and CD8 + T cells activated by IL-15 through receptor beta/common gamma signaling in trans. J Immunol 181 (2008), 8237–8247.
40. Rowley, J., Monie, A., Hung, C.F., Wu, T.C., 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 39 (2009), 491–506.
41. Rubinstein, M.P., Kovar, M., Purton, J.F., Cho, J.H., Boyman, O., Surh, C.D., et al. Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha}. Proc Natl Acad Sci U S A 103 (2006), 9166–9171.
42. Steel, J.C., Ramlogan, C.A., Yu, P., Sakai, Y., Forni, G., Waldmann, T.A., et al. Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help. Cancer Res 70 (2010), 1072–1081.
43. Stoklasek, T.A., Schluns, K.S., Lefrancois, L., Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol 177 (2006), 6072–6080.
44. Stone, J.D., Chervin, A.S., Schreiber, H., Kranz, D.M., Design and characterization of a protein superagonist of IL-15 fused with IL-15Ralpha and a high-affinity T cell receptor. Biotechnol Prog 28 (2012), 1588–1597.
45. Stonier, S.W., Schluns, K.S., Trans-presentation: a novel mechanism regulating IL-15 delivery and responses. Immunol Lett 127 (2010), 85–92.
46. Sun, H., Liu, D., IL-15/sIL-15Ralpha gene transfer suppresses Lewis lung cancer growth in the lungs, liver and kidneys. Cancer Gene Ther 23 (2016), 54–60.
47. Tosic, V., Thomas, D.L., Kranz, D.M., Liu, J., McFadden, G., Shisler, J.L., et al. Myxoma virus expressing a fusion protein of interleukin-15 (IL15) and IL15 receptor alpha has enhanced antitumor activity. PLoS One, 9, 2014, e109801.
48. Van den Bergh, J., Willemen, Y., Lion, E., Van Acker, H., De Reu, H., Anguille, S., et al. Transpresentation of interleukin-15 by IL-15/IL-15Ralpha mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity. Oncotarget 6 (2015), 44123–44133.
49. Van den Bergh, J.M., Van Tendeloo, V.F., Smits, E.L., Interleukin-15: new kid on the block for antitumor combination therapy. Cytokine Growth Factor Rev 26 (2015), 15–24.
50. Vincent, M., Bessard, A., Cochonneau, D., Teppaz, G., Sole, V., Maillasson, M., et al. Tumor targeting of the IL-15 superagonist RLI by an anti-GD2 antibody strongly enhances its antitumor potency. Int J Cancer 133 (2013), 757–765.
51. Vincent, M., Quemener, A., Jacques, Y., Antitumor activity of an immunocytokine composed of an anti-GD2 antibody and the IL-15 superagonist RLI. Oncoimmunology, 2, 2013, e26441.
52. Waldmann, T.A., The biology of IL-15: implications for cancer therapy and the treatment of autoimmune disorders. J Investig Dermatol Symp Proc 16 (2013), S28–S30.
53. Wong, H.C., Jeng, E.K., Rhode, P.R., The IL-15-based superagonist ALT-803 promotes the antigen-independent conversion of memory CD8 T cells into innate-like effector cells with antitumor activity. Oncoimmunology, 2, 2013, e26442.
54. Wu, J., IL-15 agonists: the cancer cure cytokine. J Mol Genet Med, 7, 2013, 85.
55. Wu, Z., Xu, Y., IL-15R alpha-IgG1-Fc enhances IL-2 and IL-15 anti-tumor action through NK and CD8 + T cells proliferation and activation. J Mol Cell Biol 2 (2010), 217–222.
56. Wu, Z., Xue, H.H., Bernard, J., Zeng, R., Issakov, D., Bollenbacher-Reilley, J., et al. The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15Ralpha function but is not required for trans-presentation. Blood 112 (2008), 4411–4419.
57. Xu, W., Jones, M., Liu, B., Zhu, X., Johnson, C.B., Edwards, A.C., et al. 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 73 (2013), 3075–3086.
58. Zhang, M., Ju, W., Yao, Z., Yu, P., Wei, B.R., Simpson, R.M., et al. Augmented 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 188 (2012), 6156–6164.
59. Zhu, X., Marcus, W.D., Xu, W., Lee, H.I., Han, K., Egan, J.O., et al. Novel human interleukin-15 agonists. J Immunol 183 (2009), 3598–3607.