A novel fusion of ALT-803 (interleukin (IL)-15 superagonist) with an antibody demonstrates antigen-specific antitumor responses

Journal of Biological Chemistry

Volumn 291, Issue 46, 2016, Pages 23869-23881

  Liu, Bai ^a   Kong, Lin ^a   Han, Kaiping ^a   Hong, Hao ^b   Marcus, Warren D ^a   Chen, Xiaoyue ^a   Jeng, Emily K ^a   Alter, Sarah ^a   Zhu, Xiaoyun ^a   Rubinstein, Mark P ^c   Shi, Sixiang ^b   Rhode, Peter R ^a   Cai, Weibo ^b   Wong, Hing C ^a  

^a ALTOR BIOSCIENCE CORPORATION   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGENS; BINS; CELL DEATH; CELLS; CYTOLOGY; CYTOTOXICITY; MOLECULES; MONOCLONAL ANTIBODIES; TUMORS;

ANTI-TUMOR ACTIVITIES; ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITIES; ANTIGEN PRESENTING CELLS; COMPLEMENT-DEPENDENT CYTOTOXICITIES; CYNOMOLGUS MONKEYS; IMMUNE EFFECTOR CELLS; NATURAL KILLER CELLS; THERAPEUTIC ANTIBODIES;

ANTIBODIES;

ALT 803; CD20 ANTIGEN; FC RECEPTOR; IMMUNOMODULATING AGENT; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 2 RECEPTOR BETA GAMMA C; RITUXIMAB; UNCLASSIFIED DRUG; ALT-803; HYBRID PROTEIN; IL15 PROTEIN, HUMAN; INTERLEUKIN 15; PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; B CELL LYMPHOMA; B CELL LYMPHOMA CELL; BINDING AFFINITY; BIOLOGICAL ACTIVITY; CD8+ T LYMPHOCYTE; COMPLEMENT DEPENDENT CYTOTOXICITY; CONTROLLED STUDY; HUMAN; HUMAN CELL; HUMORAL IMMUNE DEFICIENCY; IMMUNOREACTIVITY; LYMPHOCYTE PROLIFERATION; MACACA FASCICULARIS; MACROPHAGE; MALE; MOUSE; MOUSE MODEL; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; RECEPTOR BINDING; SCID MOUSE; TUMOR XENOGRAFT; AGONISTS; ANIMAL; CELLULAR IMMUNITY; CHEMISTRY; DRUG EFFECTS; DRUG SCREENING; FEMALE; GENETICS; IMMUNOLOGY; LYMPHOMA, B-CELL; PATHOLOGY; TUMOR CELL LINE;

ANIMALS; CELL LINE, TUMOR; FEMALE; HUMANS; IMMUNITY, CELLULAR; INTERLEUKIN-15; KILLER CELLS, NATURAL; LYMPHOMA, B-CELL; MICE; MICE, SCID; PROTEINS; RECOMBINANT FUSION PROTEINS; RITUXIMAB; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84994761943     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M116.733600     Document Type: Article

References (30)

1. Fehniger, T. A., and Caligiuri, M. A. (2001) Interleukin 15: biology and relevance to human disease. Blood 97, 14-32
2. Waldmann, T. A. (2006) The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat. Rev. Immunol. 6, 595-601
3. Zhu, X., Marcus, W. D., Xu, W., Lee, H. I., Han, K., Egan, J. O., Yovandich, J. L., Rhode, P. R., and Wong, H. C. (2009) Novel human interleukin-15 agonists. J. Immunol. 183, 3598-3607
4. Han, K. P., Zhu, X., Liu, B., Jeng, E., Kong, L., Yovandich, J. L., Vyas, V. V., Marcus, W. D., Chavaillaz, P. A., Romero, C. A., Rhode, P. R., and Wong, H. C. (2011) IL-15:IL-15 receptor α superagonist complex: high-level coexpression in recombinant mammalian cells, purification and characterization. Cytokine 56, 804-810
5. Xu, W., Jones, M., Liu, B., Zhu, X., Johnson, C. B., Edwards, A. C., Kong, L., Jeng, E. K., Han, K., Marcus, W. D., Rubinstein, M. P., Rhode, P. R., and Wong, H. C. (2013) Efficacy and mechanism-of-action of a novel superagonist interleukin-15:interleukin-15 receptor αSu/Fc fusion complex in syngeneic murine models of multiple myeloma. Cancer Res. 73, 3075-3086
6. Mathios, D., Park, C. K., Marcus, W. D., Alter, S., Rhode, P. R., Jeng, E. K., Wong, H. C., Pardoll, D. M., and Lim, M. (2016) 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, 187-194
7. Rosario, M., Liu, B., Kong, L., Collins, L. I., Schneider, S. E., Chen, X., Han, K., Jeng, E. K., Rhode, P. R., Leong, J. W., Schappe, T., Jewell, B. A., Keppel, C. R., Shah, K., Hess, B., et al. (2016) The IL-15-based ALT-803 complex enhances FcγRIIIa-triggered NK cell responses and in vivo clearance of B cell lymphomas. Clin. Cancer Res. 22, 596-608
8. Wong, R. L., Liu, B., Zhu, X., You, L., Kong, L., Han, K. P., Lee, H. I., Chavaillaz, P. A., Jin, M., Wang, Y., Rhode, P. R., and Wong, H. C. (2011) Interleukin-15:Interleukin-15 receptor α scaffold for creation of multivalent targeted immune molecules. Protein Eng. Des. Sel. 24, 373-383
9. Nishida, M., Usuda, S., Okabe, M., Miyakoda, H., Komatsu, M., Hanaoka, H., Teshigawara, K., and Niwa, O. (2007) Characterization of novel murine anti-CD20 monoclonal antibodies and their comparison to 2B8 and c2B8 (rituximab). Int. J. Oncol. 31, 29-40
10. Hessell, A. J., Hangartner, L., Hunter, M., Havenith, C. E., Beurskens, F. J., Bakker, J. M., Lanigan, C. M., Landucci, G., Forthal, D. N., Parren, P. W., Marx, P. A., and Burton, D. R. (2007) Fc receptor but not complement binding is important in antibody protection against HIV. Nature 449, 101-104
11. Beers, S. A., Chan, C. H., French, R. R., Cragg, M. S., and Glennie, M. J. (2010) CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin. Hematol. 47, 107-114
12. Rhode, P. R., Egan, J. O., Xu, W., Hong, H., Webb, G. M., Chen, X., Liu, B., Zhu, X., Wen, J., You, L., Kong, L., Edwards, A. C., Han, K., Shi, S., Alter, S., et al. (2016) Comparison of the superagonist complex, ALT-803, to IL15 as cancer immunotherapeutics in animal models. Cancer Immunol. Res. 4, 49-60
13. Sips, M., Krykbaeva, M., Diefenbach, T. J., Ghebremichael, M., Bowman, B. A., Dugast, A. S., Boesch, A. W., Streeck, H., Kwon, D. S., Ackerman, M. E., Suscovich, T. J., Brouckaert, P., Schacker, T. W., and Alter, G. (2016) Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies. Mucosal Immunology 10.1038/mi.2016.12
14. Abès, R., Gélizé, E., Fridman, W. H., and Teillaud, J. L. (2010) Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response. Blood 116, 926-934
15. Wang, W., Erbe, A. K., Hank, J. A., Morris, Z. S., and Sondel, P. M. (2015) NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. Front. Immunol. 6, 368
16. van Meerten, T., and Hagenbeek, A. (2010) CD20-targeted therapy: the next generation of antibodies. Semin. Hematol. 47, 199-210
17. Goede, V., Fischer, K., Busch, R., Engelke, A., Eichhorst, B., Wendtner, C. M., Chagorova, T., de la Serna, J., Dilhuydy, M. S., Illmer, T., Opat, S., Owen, C. J., Samoylova, O., Kreuzer, K. A., Stilgenbauer, S., et al. (2014) Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N. Engl. J. Med. 370, 1101-1110
18. Hillmen, P., Robak, T., Janssens, A., Babu, K. G., Kloczko, J., Grosicki, S., Doubek, M., Panagiotidis, P., Kimby, E., Schuh, A., Pettitt, A. R., Boyd, T., Montillo, M., Gupta, I. V., Wright, O., et al. (2015) Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet 385, 1873-1883
19. Ghetie, M. A., Bright, H., and Vitetta, E. S. (2001) Homodimers but not monomers of Rituxan (chimeric anti-CD20) induce apoptosis in human B-lymphoma cells and synergize with a chemotherapeutic agent and an immunotoxin. Blood 97, 1392-1398
20. Li, B., Shi, S., Qian, W., Zhao, L., Zhang, D., Hou, S., Zheng, L., Dai, J., Zhao, J., Wang, H., and Guo, Y. (2008) Development of novel tetravalent anti-CD20 antibodies with potent antitumor activity. Cancer Res. 68, 2400-2408
21. Wong, H. C., Jeng, E. K., and Rhode, P. R. (2013) 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, e26442
22. Smalls-Mantey, A., Doria-Rose, N., Klein, R., Patamawenu, A., Migueles, S. A., Ko, S. Y., Hallahan, C. W., Wong, H., Liu, B., You, L., Scheid, J., Kappes, J. C., Ochsenbauer, C., Nabel, G. J., Mascola, J. R., and Connors, M. (2012) Antibody-dependent cellular cytotoxicity against primary HIV-infected CD4+ T cells is directly associated with the magnitude of surface IgG binding. J. Virol. 86, 8672-8680
23. Seay, K., Church, C., Zheng, J. H., Deneroff, K., Ochsenbauer, C., Kappes, J. C., Liu, B., Jeng, E. K., Wong, H. C., and Goldstein, H. (2015) 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. J. Virol. 89, 6264-6274
24. Zhu, E. F., Gai, S. A., Opel, C. F., Kwan, B. H., Surana, R., Mihm, M. C., Kauke, M. J., Moynihan, K. D., Angelini, A., Williams, R. T., Stephan, M. T., Kim, J. S., Yaffe, M. B., Irvine, D. J., Weiner, L. M., et al. (2015) Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2. Cancer Cell 27, 489-501
25. Park, S., Jiang, Z., Mortenson, E. D., Deng, L., Radkevich-Brown, O., Yang, X., Sattar, H., Wang, Y., Brown, N. K., Greene, M., Liu, Y., Tang, J., Wang, S., and Fu, Y. X. (2010) The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell 18, 160-170
26. Hilchey, S. P., Hyrien, O., Mosmann, T. R., Livingstone, A. M., Friedberg, J. W., Young, F., Fisher, R. I., Kelleher, R. J., Jr., Bankert, R. B., and Bernstein, S. H. (2009) Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a "vaccinal effect" of rituximab. Blood 113, 3809-3812
27. DiLillo, D. J., and Ravetch, J. V. (2015) Differential Fc-receptor engagement drives an anti-tumor vaccinal effect. Cell 161, 1035-1045
28. Hughes, M. S., Yu, Y. Y., Dudley, M. E., Zheng, Z., Robbins, P. F., Li, Y., Wunderlich, J., Hawley, R. G., Moayeri, M., Rosenberg, S. A., and Morgan, R. A. (2005) Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions. Hum. Gene Ther. 16, 457-472
29. 64Cu-labeled anti-CD105 antibody Fab fragment. J. Nucl. Med. 56, 927-932
30. Shi, S., Hong, H., Orbay, H., Graves, S. A., Yang, Y., Ohman, J. D., Liu, B., Nickles, R. J., Wong, H. C., and Cai, W. (2015) ImmunoPET of tissue factor expression in triple-negative breast cancer with a radiolabeled antibody Fab fragment. Eur. J. Nucl. Med. Mol. Imaging 42, 1295-1303