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Ipilimumab

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Immunotherapy of Melanoma

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Abstract

Ipilimumab is the first immune check point blocker approved for the treatment of melanoma. Presently, it is the only immune based drug approved by US FDA both as an adjuvant therapy for surgically-treated ‘high-risk’ melanoma patients and as primary treatment for unresectable metastatic melanoma patients. It is a monoclonal antibody against CTLA-4, a negative regulatory receptor on T-cells. The current chapter describes potential benefits of CTLA-4 blockade by monoclonal antibodies such as ipilimumab in the treatment of melanoma. The chapter begins with an introduction of CTLA-4 receptors and the initial experiments that characterized the functions of CTLA-4 receptors. The protein structure of CTLA-4 is briefly explained followed by details on effects of CTLA-4 activation on T-cells and then by the details of downstream signaling events that follow the activation of CTLA-4 receptors. Next, the description of marketed ipilimumab formulation (Yervoy) is given along with the details of its clinical pharmacology. The mechanism of action of ipilimumab is then described followed by discussion on results from clinical trials that demonstrated the benefits of ipilimumab in treatment of patients with unresectable metastatic melanoma. Next, the adverse effects of ipilimumab are discussed along with a note on possible drug interactions and contraindications. Finally, towards the end of the chapter, the major limitations of ipilimumab are described.

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References

  1. Brunet, J. F., Denizot, F., Luciani, M. F., Roux-Dosseto, M., Suzan, M., Mattei, M. G., et al. (1987). A new member of the immunoglobulin superfamily–CTLA-4. Nature, 328(6127), 267–270. doi:10.1038/328267a0

    Article  CAS  PubMed  Google Scholar 

  2. Dariavach, P., Mattei, M. G., Golstein, P., & Lefranc, M. P. (1988). Human Ig superfamily CTLA-4 gene: Chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. European Journal of Immunology, 18(12), 1901–1905. doi:10.1002/eji.1830181206

    Article  CAS  PubMed  Google Scholar 

  3. Harper, K., Balzano, C., Rouvier, E., Mattei, M. G., Luciani, M. F., & Golstein, P. (1991). CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location. The Journal of Immunology, 147(3), 1037–1044.

    CAS  PubMed  Google Scholar 

  4. Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., & Ledbetter, J. A. (1991). CTLA-4 is a second receptor for the B cell activation antigen B7. Journal of Experimental Medicine, 174(3), 561–569.

    Article  CAS  PubMed  Google Scholar 

  5. Linsley, P. S., Greene, J. L., Tan, P., Bradshaw, J., Ledbetter, J. A., Anasetti, C., et al. (1992). Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. Journal of Experimental Medicine, 176(6), 1595–1604.

    Article  CAS  PubMed  Google Scholar 

  6. Walunas, T. L., Lenschow, D. J., Bakker, C. Y., Linsley, P. S., Freeman, G. J., Green, J. M., et al. (1994). CTLA-4 can function as a negative regulator of T cell activation. Immunity, 1(5), 405–413. (1074-7613(94)90071-X [pii]).

    Article  CAS  PubMed  Google Scholar 

  7. Krummel, M. F., & Allison, J. P. (1995). CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. Journal of Experimental Medicine, 182(2), 459–465.

    Article  CAS  PubMed  Google Scholar 

  8. Krummel, M. F., & Allison, J. P. (1996). CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. Journal of Experimental Medicine, 183(6), 2533–2540.

    Article  CAS  PubMed  Google Scholar 

  9. Walunas, T. L., Bakker, C. Y., & Bluestone, J. A. (1996). CTLA-4 ligation blocks CD28-dependent T cell activation. Journal of Experimental Medicine, 183(6), 2541–2550.

    Article  CAS  PubMed  Google Scholar 

  10. Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., et al. (1995). Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science, 270(5238), 985–988.

    Article  CAS  PubMed  Google Scholar 

  11. Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995). Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity, 3(5), 541–547.

    Article  CAS  PubMed  Google Scholar 

  12. Chambers, C. A., Cado, D., Truong, T., & Allison, J. P. (1997). Thymocyte development is normal in CTLA-4-deficient mice. Proceedings of the National Academy of Sciences of the USA, 94(17), 9296–9301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chambers, C. A., Sullivan, T. J., & Allison, J. P. (1997). Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells. Immunity, 7(6), 885–895. (S1074-7613(00)80406-9 [pii]).

    Article  CAS  PubMed  Google Scholar 

  14. Waterhouse, P., Bachmann, M. F., Penninger, J. M., Ohashi, P. S., & Mak, T. W. (1997). Normal thymic selection, normal viability and decreased lymphoproliferation in T cell receptor-transgenic CTLA-4-deficient mice. European Journal of Immunology, 27(8), 1887–1892. doi:10.1002/eji.1830270811

    Article  CAS  PubMed  Google Scholar 

  15. Leach, D. R., Krummel, M. F., & Allison, J. P. (1996). Enhancement of antitumor immunity by CTLA-4 blockade. Science, 271(5256), 1734–1736.

    Article  CAS  PubMed  Google Scholar 

  16. Weber, J. (2010). Immune checkpoint proteins: a new therapeutic paradigm for cancer–preclinical background: CTLA-4 and PD-1 blockade. Seminars in Oncology, 37(5), 430–439. doi:10.1053/j.seminoncol.2010.09.005 (S0093-7754(10)00159-4 [pii]).

    Article  CAS  PubMed  Google Scholar 

  17. Funt, S. A., Page, D. B., Wolchok, J. D., & Postow, M. A. (2014). CTLA-4 antibodies: new directions, new combinations. Oncology (Williston Park), 28(Suppl 3), 6–14. (202325 [pii]).

    Google Scholar 

  18. Grosso, J. F., & Jure-Kunkel, M. N. (2013). CTLA-4 blockade in tumor models: An overview of preclinical and translational research. Cancer Immunity, 13, 5.

    PubMed  PubMed Central  Google Scholar 

  19. Graca, L. (2008). CTLA4Ig and the therapeutic potential of T cell co-stimulation blockade. Acta Reumatolgica Portuguesa, 33(3), 267–276.

    Google Scholar 

  20. Camacho, L. H. (2015). CTLA-4 blockade with ipilimumab: Biology, safety, efficacy, and future considerations. Cancer Medicine, 4(5), 661–672. doi:10.1002/cam4.371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Camacho, L. H., Antonia, S., Sosman, J., Kirkwood, J. M., Gajewski, T. F., Redman, B., et al. (2009). Phase I/II trial of tremelimumab in patients with metastatic melanoma. Journal of Clinical Oncology, 27(7), 1075–1081. doi:10.1200/JCO.2008.19.2435 (JCO.2008.19.2435 [pii]).

    Article  CAS  PubMed  Google Scholar 

  22. Ribas, A., Camacho, L. H., Lopez-Berestein, G., Pavlov, D., Bulanhagui, C. A., Millham, R., et al. (2005). Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. Journal of Clinical Oncology, 23(35), 8968–8977. doi:10.1200/JCO.2005.01.109 (JCO.2005.01.109 [pii]).

    Article  CAS  PubMed  Google Scholar 

  23. Ribas, A., Kefford, R., Marshall, M. A., Punt, C. J., Haanen, J. B., Marmol, M., et al. (2013). Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. Journal of Clinical Oncology, 31(5), 616–622. doi:10.1200/JCO.2012.44.6112 (JCO.2012.44.6112 [pii]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kapadia, D., & Fong, L. (2005). CTLA-4 blockade: Autoimmunity as treatment. Journal of Clinical Oncology, 23(35), 8926–8928. doi:10.1200/JCO.2005.07.012 (JCO.2005.07.012 [pii]).

    Article  CAS  PubMed  Google Scholar 

  25. Rotte, A., Bhandaru, M., Zhou, Y., & McElwee, K. J. (2015). Immunotherapy of melanoma: Present options and future promises. Cancer and Metastasis Reviews, 34(1), 115–128. doi:10.1007/s10555-014-9542-0

    Article  CAS  PubMed  Google Scholar 

  26. FDA approves Yervoy to reduce the risk of melanoma returning after surgery. (2015). FDA news release, October 28, 2015.

    Google Scholar 

  27. Metzler, W. J., Bajorath, J., Fenderson, W., Shaw, S. Y., Constantine, K. L., Naemura, J., et al. (1997). Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28. Natural Structural Biology, 4(7), 527–531.

    Article  CAS  Google Scholar 

  28. Ostrov, D. A., Shi, W., Schwartz, J. C., Almo, S. C., & Nathenson, S. G. (2000). Structure of murine CTLA-4 and its role in modulating T cell responsiveness. Science, 290(5492), 816–819. (8944 [pii]).

    Article  CAS  PubMed  Google Scholar 

  29. Schwartz, J. C., Zhang, X., Fedorov, A. A., Nathenson, S. G., & Almo, S. C. (2001). Structural basis for co-stimulation by the human CTLA-4/B7-2 complex. Nature, 410(6828), 604–608. doi:10.1038/35069112 (35069112 [pii]).

    Article  CAS  PubMed  Google Scholar 

  30. Stamper, C. C., Zhang, Y., Tobin, J. F., Erbe, D. V., Ikemizu, S., Davis, S. J., et al. (2001). Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature, 410(6828), 608–611. doi:10.1038/35069118 (35069118 [pii]).

    Article  CAS  PubMed  Google Scholar 

  31. Intlekofer, A. M., & Thompson, C. B. (2013). At the bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. Journal of Leukocyte Biology, 94(1), 25–39. doi:10.1189/jlb.1212621 (jlb.1212621 [pii]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Perkins, D., Wang, Z., Donovan, C., He, H., Mark, D., Guan, G., et al. (1996). Regulation of CTLA-4 expression during T cell activation. The Journal of Immunology, 156(11), 4154–4159.

    CAS  PubMed  Google Scholar 

  33. Alegre, M. L., Noel, P. J., Eisfelder, B. J., Chuang, E., Clark, M. R., Reiner, S. L., et al. (1996). Regulation of surface and intracellular expression of CTLA4 on mouse T cells. The Journal of Immunology, 157(11), 4762–4770.

    CAS  PubMed  Google Scholar 

  34. Carreno, B. M., Bennett, F., Chau, T. A., Ling, V., Luxenberg, D., Jussif, J., et al. (2000). CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression. The Journal of Immunology, 165(3), 1352–1356. (ji_v165n3p1352 [pii]).

    Article  CAS  PubMed  Google Scholar 

  35. Chikuma, S., Abbas, A. K., & Bluestone, J. A. (2005). B7-independent inhibition of T cells by CTLA-4. The Journal of Immunology, 175(1), 177–181. (175/1/177 [pii]).

    Article  CAS  PubMed  Google Scholar 

  36. Masteller, E. L., Chuang, E., Mullen, A. C., Reiner, S. L., & Thompson, C. B. (2000). Structural analysis of CTLA-4 function in vivo. The Journal of Immunology, 164(10), 5319–5327. (ji_v164n10p5319 [pii]).

    Article  CAS  PubMed  Google Scholar 

  37. Chikuma, S., Imboden, J. B., & Bluestone, J. A. (2003). Negative regulation of T cell receptor-lipid raft interaction by cytotoxic T lymphocyte-associated antigen 4. Journal of Experimental Medicine, 197(1), 129–135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schneider, H., Smith, X., Liu, H., Bismuth, G., & Rudd, C. E. (2008). CTLA-4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times and calcium mobilization. European Journal of Immunology, 38(1), 40–47. doi:10.1002/eji.200737423

    Article  CAS  PubMed  Google Scholar 

  39. Yokosuka, T., Kobayashi, W., Takamatsu, M., Sakata-Sogawa, K., Zeng, H., Hashimoto-Tane, A., et al. (2010). Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation. Immunity, 33(3), 326–339. doi:10.1016/j.immuni.2010.09.006 (S1074-7613(10)00329-8 [pii]).

    Article  CAS  PubMed  Google Scholar 

  40. Schneider, H., Downey, J., Smith, A., Zinselmeyer, B. H., Rush, C., Brewer, J. M., et al. (2006). Reversal of the TCR stop signal by CTLA-4. Science, 313(5795), 1972–1975. doi:10.1126/science.1131078 (1131078 [pii]).

    Article  CAS  PubMed  Google Scholar 

  41. Li, D., Gal, I., Vermes, C., Alegre, M. L., Chong, A. S., Chen, L., et al. (2004). Cutting edge: Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. The Journal of Immunology, 173(12), 7135–7139. (173/12/7135 [pii]).

    Article  CAS  PubMed  Google Scholar 

  42. Schneider, H., Valk, E., Leung, R., & Rudd, C. E. (2008). CTLA-4 activation of phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death. PLoS ONE, 3(12), e3842. doi:10.1371/journal.pone.0003842

    Article  PubMed  PubMed Central  Google Scholar 

  43. Fraser, J. H., Rincon, M., McCoy, K. D., & Le Gros, G. (1999). CTLA4 ligation attenuates AP-1, NFAT and NF-kappaB activity in activated T cells. European Journal of Immunology, 29(3), 838–844. doi:10.1002/(SICI)1521-4141(199903)29:03<838:AID-IMMU838>3.0.CO;2-P ([pii]).

    Article  CAS  PubMed  Google Scholar 

  44. Olsson, C., Riesbeck, K., Dohlsten, M., & Michaelsson, E. (1999). CTLA-4 ligation suppresses CD28-induced NF-kappaB and AP-1 activity in mouse T cell blasts. Journal of Biological Chemistry, 274(20), 14400–14405.

    Article  CAS  PubMed  Google Scholar 

  45. Yervoy package insert. Product Information: Bristol-Myers Squibb.

    Google Scholar 

  46. Weber, J. S., O’Day, S., Urba, W., Powderly, J., Nichol, G., Yellin, M., et al. (2008). Phase I/II study of ipilimumab for patients with metastatic melanoma. Journal of Clinical Oncology, 26(36), 5950–5956. doi:10.1200/JCO.2008.16.1927 (JCO.2008.16.1927 [pii]).

    Article  CAS  PubMed  Google Scholar 

  47. Wolchok, J. D., Yang, A. S., & Weber, J. S. (2010). Immune regulatory antibodies: Are they the next advance? Cancer Journal, 16(4), 311–317. doi:10.1097/PPO.0b013e3181eb3381 (00130404-201007000-00005 [pii]).

    Article  CAS  Google Scholar 

  48. Melero, I., Hervas-Stubbs, S., Glennie, M., Pardoll, D. M., & Chen, L. (2007). Immunostimulatory monoclonal antibodies for cancer therapy. Nature Reviews Cancer, 7(2), 95–106. doi:10.1038/nrc2051 (nrc2051 [pii]).

    Article  CAS  PubMed  Google Scholar 

  49. Linsley, P. S., Bradshaw, J., Greene, J., Peach, R., Bennett, K. L., & Mittler, R. S. (1996). Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity, 4(6), 535–543. (S1074-7613(00)80480-X [pii]).

    Article  CAS  PubMed  Google Scholar 

  50. Collins, A. V., Brodie, D. W., Gilbert, R. J., Iaboni, A., Manso-Sancho, R., Walse, B., et al. (2002). The interaction properties of costimulatory molecules revisited. Immunity, 17(2), 201–210. (S107476130200362X [pii]).

    Article  CAS  PubMed  Google Scholar 

  51. Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., et al. (2008). CTLA-4 control over Foxp3+ regulatory T cell function. Science, 322(5899), 271–275. doi:10.1126/science.1160062 (322/5899/271 [pii]).

    Article  CAS  PubMed  Google Scholar 

  52. Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., et al. (2003). Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proceedings of the National Academy of Sciences of the USA, 100(14), 8372–8377. doi:10.1073/pnas.1533209100 (1533209100 [pii]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Shrikant, P., Khoruts, A., & Mescher, M. F. (1999). CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism. Immunity, 11(4), 483–493. (S1074-7613(00)80123-5 [pii]).

    Article  CAS  PubMed  Google Scholar 

  54. Weber, J. (2008). Overcoming immunologic tolerance to melanoma: Targeting CTLA-4 with ipilimumab (MDX-010). Oncologist, 13(Suppl 4), 16–25. doi:10.1634/theoncologist.13-S4-16 (13/suppl_4/16 [pii]).

    Article  CAS  PubMed  Google Scholar 

  55. Yang, J. C., Hughes, M., Kammula, U., Royal, R., Sherry, R. M., Topalian, S. L., et al. (2007). Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. Journal of Immunotherapy, 30(8), 825–830. doi:10.1097/CJI.0b013e318156e47e (00002371-200711000-00005 [pii]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. van Elsas, A., Hurwitz, A. A., & Allison, J. P. (1999). Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. Journal of Experimental Medicine, 190(3), 355–366.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Hodi, F. S., Mihm, M. C., Soiffer, R. J., Haluska, F. G., Butler, M., Seiden, M. V., et al. (2003). Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proceedings of the National Academy of Sciences of the USA, 100(8), 4712–4717. doi:10.1073/pnas.0830997100 (0830997100 [pii]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., et al. (2005). Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. Journal of Clinical Oncology, 23(25), 6043–6053. doi:10.1200/JCO.2005.06.205 (JCO.2005.06.205 [pii]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wolchok, J. D., Neyns, B., Linette, G., Negrier, S., Lutzky, J., Thomas, L., et al. (2010). Ipilimumab monotherapy in patients with pretreated advanced melanoma: A randomised, double-blind, multicentre, phase 2, dose-ranging study. The Lancet Oncology, 11(2), 155–164. doi:10.1016/S1470-2045(09)70334-1 (S1470-2045(09)70334-1 [pii]).

    Article  CAS  PubMed  Google Scholar 

  60. O’Day, S. J., Maio, M., Chiarion-Sileni, V., Gajewski, T. F., Pehamberger, H., Bondarenko, I. N., et al. (2010). Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: A multicenter single-arm phase II study. Annals of Oncology, 21(8), 1712–1717. doi:10.1093/annonc/mdq013 (mdq013 [pii]).

    Article  PubMed  Google Scholar 

  61. Fellner, C. (2012). Ipilimumab (yervoy) prolongs survival in advanced melanoma: Serious side effects and a hefty price tag may limit its use. Pharmacy and Therapeutics, 37(9), 503–530.

    PubMed  PubMed Central  Google Scholar 

  62. Hodi, F. S., O’Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., et al. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine, 363(8), 711–723. doi:10.1056/NEJMoa1003466 (NEJMoa1003466 [pii]).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Robert, C., Thomas, L., Bondarenko, I., O’Day, S., Weber, J., Garbe, C., et al. (2011). Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. New England Journal of Medicine, 364(26), 2517–2526. doi:10.1056/NEJMoa1104621

    Article  CAS  PubMed  Google Scholar 

  64. Kaufman, H. L., Kirkwood, J. M., Hodi, F. S., Agarwala, S., Amatruda, T., Bines, S. D., et al. (2013). The Society for Immunotherapy of Cancer consensus statement on tumour immunotherapy for the treatment of cutaneous melanoma. Nature Reviews Clinical Oncology, 10(10), 588–598. doi:10.1038/nrclinonc.2013.153 (nrclinonc.2013.153 [pii]).

    Article  CAS  PubMed  Google Scholar 

  65. Bertrand, A., Kostine, M., Barnetche, T., Truchetet, M. E., & Schaeverbeke, T. (2015). Immune related adverse events associated with anti-CTLA-4 antibodies: Systematic review and meta-analysis. BMC Medicine, 13, 211. doi:10.1186/s12916-015-0455-8 (10.1186/s12916-015-0455-8 [pii]).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Buchbinder, E. I., & McDermott, D. F. (2015). Cytotoxic T-lymphocyte antigen-4 blockade in melanoma. Clinical Therapeutics, 37(4), 755–763. doi:10.1016/j.clinthera.2015.02.003 (S0149-2918(15)00069-7 [pii]).

    Article  CAS  PubMed  Google Scholar 

  67. Buchbinder, E., & Hodi, F. S. (2015). Cytotoxic T lymphocyte antigen-4 and immune checkpoint blockade. The Journal of Clinical Investigation, 125(9), 3377–3383. doi:10.1172/JCI80012 (80012 [pii]).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Weber, J. (2007). Review: Anti-CTLA-4 antibody ipilimumab: Case studies of clinical response and immune-related adverse events. Oncologist, 12(7), 864–872. doi:10.1634/theoncologist.12-7-864 (12/7/864 [pii]).

    Article  CAS  PubMed  Google Scholar 

  69. Della Vittoria Scarpati, G., Fusciello, C., Perri, F., Sabbatino, F., Ferrone, S., Carlomagno, C., et al. (2014). Ipilimumab in the treatment of metastatic melanoma: Management of adverse events. Journal of Onco Targets and Therapy, 7, 203–209, doi:10.2147/OTT.S57335 (ott-7-203 [pii]).

  70. Culver, M. E., Gatesman, M. L., Mancl, E. E., & Lowe, D. K. (2011). Ipilimumab: A novel treatment for metastatic melanoma. Annals of Pharmacotherapy, 45(4), 510–519. doi:10.1345/aph.1P651 (aph.1P651 [pii]).

    Article  CAS  PubMed  Google Scholar 

  71. Chustecka, Z. (2011). Ipilimumab for melanoma approved in Europe.

    Google Scholar 

  72. Chustecka, Z. (2015). New Immunotherapy costing $1 million a year.

    Google Scholar 

  73. Pharmacoeconomic evaluation of ipilimumab (Yervoy) for the treatment of advanced (unresectable or metastatic) melanoma in adult patients who have received prior therapy. September 2011 (2011). In N. C. f. Pharmacoeconomics (Ed.). Ireland.

    Google Scholar 

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  1. Faculty of Medicine, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada

    Anand Rotte & Madhuri Bhandaru

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Rotte, A., Bhandaru, M. (2016). Ipilimumab. In: Immunotherapy of Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-48066-4_11

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