ASH Clinical News December 2014 | Page 62

Despite recent advances, multiple myeloma remains a largely incurable disease, with fewer than half of patients surviving five years after diagnosis.23 We need a new approach. Bristol-Myers Squibb is deeply committed to furthering the science behind immuno-oncology. Leading the way in immuno-oncology research, Bristol-Myers Squibb is investigating the potential of the SLAMF7, KIR, and CD137 pathways to activate the body’s own Natural Killer Cells to target myeloma cells. REFERENCES: 1. Cheng M et al. NK cell-based immunotherapy for malignant disease. Cell Molec Immunol. 2013;10:230-252. 2. Jurisic V et al. Med Oncol. 2007;24:312-317. 3. Marcus A et al. Adv Immunol. 2014;122:91-128. 4. Vivier E et al. Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol. 2012;12:239-252. 5. Carbone E et al. Blood. 2005;105:251-258. 6. Frohn C et al. Br J Haematol. 2002;119:660-664. 7. Teh BW et al. Changing treatment paradigms for patients with plasma cell myeloma: Impact upon immune determinants of infection. Blood Rev. 2014;28:75-86. 8. Bernal M et al. Changes in activatory and inhibitory natural killer (NK) receptors may induce progression to multiple myeloma : Implications for tumor evasion of T and NK cells. Human Immunol. 2009;70:854-857. 9. Jinushi M et al. MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma. Proc Natl Acad Sci USA. 2008;105:1285-1290. 10. von Lilienfeld-Toal M et al. Reduced immune effector cell NKG2D expression and increased levels of soluble NKG2D ligands in multiple myeloma may not be causally linked. Cancer Immunol Immunother. 2010;59:829-839. 11. Cook G et al. Transforming growth factor ß from multiple myeloma cells inhibits proliferation and IL-2 responsiveness in T lymphocytes. J Leukoc Biol. 1999;66:981-988. 12. Yu J et al. Pro- and anti-inflammatory cytokine signaling: reciprocal antagonism regulates interferon-gamma production by human natural killer cells. Immunity. 2006;24:575-590. 13. Nielsen H et al. Immune dysfunction in multiple myeloma. Reduced natural killer cell activity and increased levels of soluble interleukin-2 receptors. APMIS. 1991;99:340-346. 14. Tinhofer I et al. Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma. Blood. 2000;95:610-618. 15. Cruz-Munoz ME et al. Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function. Nat Immunol. 2009;10:297-305. 16. Campbell KS and Purdy AK. Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations. Immunology. 2011;132:312-325. 17. Murillo O et al. Therapeutic antitumor efficacy of anti-CD137 agonistic monoclonal antibody in mouse models of myeloma. Clin Cancer Res. 2008;14:68956906. 18. Caligiuri MA. Blood. 2008;112:461-469. 19. Mace EM et al. Immunol Cell Biol. 2014;92:245-255. 20. Krzewski H and Coligan JE. Front Immunol. 2012;3:335. 21. Bae J, Prabhala RH, Munshi NC. Dendritic cells and peptide-based vaccine in multiple myeloma. In: Munshi NC, Anderson KC, eds. Advances in Biology and Therapy of Multiple Myeloma, Volume 2: Translational and Clinical Research. New York, NY: Springer; 2013:131-150. 22. Gullo C et al. PLoS One. 2010;5:e10845. 23. SEER Stat Fact Sheets: Myeloma, 2004-2010. http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed September 4, 2014. © 2014 Bristol-Myers Squibb Company. All rights reserved. ONCUS14UB02095-02-01 10/14