Combination immunotherapy: A road map

Journal for ImmunoTherapy of Cancer

Volumn 5, Issue 1, 2017, Pages

  Ott, Patrick A ^a   Hodi, F Stephen ^a   Kaufman, Howard L ^b   Wigginton, Jon M ^c   Wolchok, Jedd D ^d  

^a HARVARD MEDICAL SCHOOL   (United States)

^b RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^c Analytical Sciences   (United States)

^d MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Checkpoint inhibitors; Clinical trial; Combination; Endpoints; Immunotherapy; Preclinical models

Indexed keywords

CD134 ANTIGEN; CD137 ANTIGEN; CD40 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GLUCOCORTICOID INDUCED TUMOR NECROSIS FACTOR RECEPTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IPILIMUMAB; MONOCLONAL ANTIBODY; NIVOLUMAB; ONCOLYTIC VIRUS; PEMBROLIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; TALIMOGENE LAHERPAREPVEC; VACCINE; ANTINEOPLASTIC AGENT; IMMUNOLOGICAL ANTINEOPLASTIC AGENT;

ANGIOGENESIS; ANTIGEN PRESENTATION; ANTINEOPLASTIC ACTIVITY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CELL CYCLE CHECKPOINT; CELLULAR IMMUNITY; CLINICAL TRIAL; DISEASE SIMULATION; DRUG EFFICACY; DRUG SAFETY; GENE INACTIVATION; HUMAN; MAXIMUM TOLERATED DOSE; MELANOMA; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; NON SMALL CELL LUNG CANCER; NONHUMAN; PATIENT SAFETY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; TUMOR REGRESSION; ANIMAL; CLINICAL TRIAL (TOPIC); IMMUNOTHERAPY; NEOPLASM;

ANIMALS; ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOTHERAPY; NEOPLASMS;

EID: 85013344100     PISSN: None     EISSN: 20511426     Source Type: Journal    
DOI: 10.1186/s40425-017-0218-5     Document Type: Review

References (107)

1. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56-61. doi: 10.1126/science.aaa8172.
2. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-23. doi: 10.1056/NEJMoa1003466.
3. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517-26. doi: 10.1056/NEJMoa1104621.
4. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-54. doi: 10.1056/NEJMoa1200690.
5. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455-65. doi: 10.1056/NEJMoa1200694.
6. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018-28. doi: 10.1056/NEJMoa1501824.
7. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124-8. doi: 10.1126/science.aaa1348.
8. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-20. doi: 10.1056/NEJMoa1500596.
9. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350(6257):207-11. doi: 10.1126/science.aad0095.
10. Chen J, Creasy C, Torres-Cabala CA, Ekmekcioglu S, Maiti SN, Kale C, et al. Predictive immune biomarker signatures in the tumor microenvironment of melanoma metastases associated with tumor-infiltrating lymphocyte (TIL) therapy. J Immunother Cancer. 2014;2 Suppl 3:P243-P. doi: 10.1186/2051-1426-2-S3-P243.
11. Chen PL, Roh W, Reuben A, Cooper ZA, Spencer CN, Prieto PA, et al. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. Cancer Discov. 2016;6(8):827-37. doi: 10.1158/2159-8290.cd-15-1545.
12. Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature. 2015;523:231-5. doi: 10.1038/nature14404.
13. Snyder A, Wolchok JD, Chan TA. Genetic basis for clinical response to CTLA-4 blockade. N Engl J Med. 2015;372(8):783. doi: 10.1056/NEJMc1415938.
14. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69-74. doi: 10.1126/science.aaa4971.
15. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33:2780-8. doi: 10.1200/JCO.2014.58.3377.
16. Puzanov I, Milhem MM, Minor D, Hamid O, Li A, Chen L, et al. Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol. 2016;34(22):2619-26. doi: 10.1200/jco.2016.67.1529.
17. Long GV. Primary analysis of MASTERKEY-265 phase 1b study of talimogene laherparepvec (T-VEC) and pembrolizumab (pembro) for unresectable stage IIIB-IV melanoma. Society for Melanoma Research 2015 Congress. 2015;November 18-21(San Fransciso, California).
18. Goodwin RG, Din WS, Davis-Smith T, Anderson DM, Gimpel SD, Sato TA, et al. Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor. Eur J Immunol. 1993;23(10):2631-41. doi: 10.1002/eji.1830231037.
19. Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, et al. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res. 2013;73(24):7189-98. doi: 10.1158/0008-5472.CAN-12-4174.
20. Melero I, Hirschhorn-Cymerman D, Morales-Kastresana A, Sanmamed MF, Wolchok JD. Agonist antibodies to TNFR molecules that costimulate T and NK cells. Clin Cancer Res. 2013;19(5):1044-53. doi: 10.1158/1078-0432.CCR-12-2065.
21. Wei H, Zhao L, Li W, Fan K, Qian W, Hou S, et al. Combinatorial PD-1 blockade and CD137 activation has therapeutic efficacy in murine cancer models and synergizes with cisplatin. PLoS One. 2013;8(12):e84927. doi: 10.1371/journal.pone.0084927.
22. Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol. 2010;37(5):508-16. doi: 10.1053/j.seminoncol.2010.09.008.
23. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507-17. doi: 10.1056/NEJMoa1407222.
24. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725-33. doi: 10.1056/NEJMoa1103849.
25. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015;348(6230):62-8. doi: 10.1126/science.aaa4967.
26. Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010;107(9):4275-80. doi: 10.1073/pnas.0915174107.
27. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23-34. doi: 10.1056/NEJMoa1504030.
28. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372(21):2006-17. doi: 10.1056/NEJMoa1414428.
29. Hu-Lieskovan S, Robert L, Homet Moreno B, Ribas A. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J Clin Oncol. 2014;32(21):2248-54. doi: 10.1200/JCO.2013.52.1377.
30. Frederick DT, Piris A, Cogdill AP, Cooper ZA, Lezcano C, Ferrone CR, et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res. 2013;19(5):1225-31. doi: 10.1158/1078-0432.CCR-12-1630.
31. Kandalaft LE, Motz GT, Busch J, Coukos G. Angiogenesis and the tumor vasculature as antitumor immune modulators: the role of vascular endothelial growth factor and endothelin. Curr Top Microbiol Immunol. 2011;344:129-48. doi: 10.1007/82_2010_95.
32. Ohm JE, Carbone DP. VEGF as a mediator of tumor-associated immunodeficiency. Immunol Res. 2001;23(2-3):263-72. doi: 10.1385/IR:23:2-3:263.
33. Ott PA, Hodi FS, Buchbinder EI. Inhibition of immune checkpoints and vascular endothelial growth factor as combination therapy for metastatic melanoma: an overview of rationale, preclinical evidence, and initial clinical data. Front Oncol. 2015;5:202. doi: 10.3389/fonc.2015.00202.
34. Hodi FS, Lawrence D, Lezcano C, Wu X, Zhou J, Sasada T, et al. Bevacizumab plus ipilimumab in patients with metastatic melanoma. Cancer Immunol Res. 2014;2(7):632-42. doi: 10.1158/2326-6066.CIR-14-0053.
35. Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013;105(4):256-65. doi: 10.1093/jnci/djs629.
36. Demaria S, Kawashima N, Yang AM, Devitt ML, Babb JS, Allison JP, et al. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res. 2005;11(2 Pt 1):728-34.
37. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009;15(17):5379-88. doi: 10.1158/1078-0432.CCR-09-0265.
38. Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366(10):925-31. doi: 10.1056/NEJMoa1112824.
39. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520(7547):373-7. doi: 10.1038/nature14292.
40. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med. 1999;189(9):1363-72.
41. Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, et al. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest. 2007;117(9):2570-82. doi: 10.1172/JCI31911.
42. Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ, et al. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest. 2004;114(2):280-90. doi: 10.1172/JCI21583.
43. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9(10):1269-74. doi: 10.1038/nm934.
44. Taylor MW, Feng GS. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991;5(11):2516-22.
45. Incyte. Incyte and Merck to Advance Clinical Development Program Investigating the Combination of Epacadostat with KEYTRUDA® (pembrolizumab). January 9, 2017. http://www.incyte.com/media/recent-news.aspx. Accessed 23 Jan 2017.
46. Zitvogel L, Kepp O, Kroemer G. Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol. 2011;8(3):151-60. doi: 10.1038/nrclinonc.2010.223.
47. Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992;176(6):1693-702.
48. Paquette RL, Hsu NC, Kiertscher SM, Park AN, Tran L, Roth MD, et al. Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells. J Leukoc Biol. 1998;64(3):358-67.
49. Hodi FS, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, et al. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014;312(17):1744-53. doi: 10.1001/jama.2014.13943.
50. Tarhini AA, Cherian J, Moschos SJ, Tawbi HA, Shuai Y, Gooding WE, et al. Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma. J Clin Oncol. 2012;30(3):322-8. doi: 10.1200/JCO.2011.37.5394.
51. Maker AV, Phan GQ, Attia P, Yang JC, Sherry RM, Topalian SL, et al. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol. 2005;12(12):1005-16. doi: 10.1245/aso.2005.03.536.
52. Devaud C, Westwood JA, John LB, Flynn JK, Paquet-Fifield S, Duong CP, et al. Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy. Mol Ther. 2014;22(1):18-27. doi: 10.1038/mt.2013.219.
53. Dranoff G. Experimental mouse tumour models: what can be learnt about human cancer immunology? Nat Rev Immunol. 2012;12(1):61-6. doi: 10.1038/nri3129.
54. DuPage M, Jacks T. Genetically engineered mouse models of cancer reveal new insights about the antitumor immune response. Curr Opin Immunol. 2013;25(2):192-9. doi: 10.1016/j.coi.2013.02.005.
55. Fantozzi A, Christofori G. Mouse models of breast cancer metastasis. Breast Cancer Res. 2006;8(4):212. doi: 10.1186/bcr1530.
56. Eyles J, Puaux AL, Wang X, Toh B, Prakash C, Hong M, et al. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J Clin Invest. 2010;120(6):2030-9. doi: 10.1172/jci42002.
57. Knight DA, Ngiow SF, Li M, Parmenter T, Mok S, Cass A, et al. Host immunity contributes to the anti-melanoma activity of BRAF inhibitors. J Clin Invest. 2016;126(1):402-3. doi: 10.1172/jci84828.
58. Kato M, Takahashi M, Akhand AA, Liu W, Dai Y, Shimizu S, et al. Transgenic mouse model for skin malignant melanoma. Oncogene. 1998;17(14):1885-8. doi: 10.1038/sj.onc.1202077.
59. DuPage M, Cheung AF, Mazumdar C, Winslow MM, Bronson R, Schmidt LM, et al. Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression. Cancer Cell. 2011;19(1):72-85. doi: 10.1016/j.ccr.2010.11.011.
60. DuPage M, Mazumdar C, Schmidt LM, Cheung AF, Jacks T. Expression of tumour-specific antigens underlies cancer immunoediting. Nature. 2012;482(7385):405-9. doi: 10.1038/nature10803.
61. Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R, Magrini VJ, et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature. 2012;482(7385):400-4. doi: 10.1038/nature10755.
62. Flanagan SP. 'Nude', a new hairless gene with pleiotropic effects in the mouse. Genet Res. 1966;8(3):295-309.
63. Balciunaite G, Keller MP, Balciunaite E, Piali L, Zuklys S, Mathieu YD, et al. Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat Immunol. 2002;3(11):1102-8. doi: 10.1038/ni850.
64. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992;68(5):869-77.
65. Xie Y, Akpinarli A, Maris C, Hipkiss EL, Lane M, Kwon EK, et al. Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma. J Exp Med. 2010;207(3):651-67. doi: 10.1084/jem.20091921.
66. Goding SR, Wilson KA, Xie Y, Harris KM, Baxi A, Akpinarli A, et al. Restoring immune function of tumor-specific CD4+ T cells during recurrence of melanoma. J Immunol. 2013;190(9):4899-909. doi: 10.4049/jimmunol.1300271.
67. Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman DR, et al. CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol. 2005;174(5):2591-601.
68. Finnie NJ, Gottlieb TM, Blunt T, Jeggo PA, Jackson SP. DNA-dependent protein kinase activity is absent in xrs-6 cells: implications for site-specific recombination and DNA double-strand break repair. Proc Natl Acad Sci U S A. 1995;92(1):320-4.
69. Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM, Carter T, et al. DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science. 1995;267(5201):1178-83.
70. Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174(10):6477-89.
71. Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor chain(null) mice. Blood. 2005;106(5):1565-73. doi: 10.1182/blood-2005-02-0516.
72. Ito R, Takahashi T, Katano I, Ito M. Current advances in humanized mouse models. Cell Mol Immunol. 2012;9(3):208-14. doi: 10.1038/cmi.2012.2.
73. Overwijk WW, Lee DS, Surman DR, Irvine KR, Touloukian CE, Chan CC, et al. Vaccination with a recombinant vaccinia virus encoding a "self" antigen induces autoimmune vitiligo and tumor cell destruction in mice: requirement for CD4(+) T lymphocytes. Proc Natl Acad Sci U S A. 1999;96(6):2982-7.
74. Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med. 2014;6(230):230ra45. doi: 10.1126/scitranslmed.3008002.
75. Teng MW, Ngiow SF, von Scheidt B, McLaughlin N, Sparwasser T, Smyth MJ. Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth. Cancer Res. 2010;70(20):7800-9. doi: 10.1158/0008-5472.can-10-1681.
76. Lahl K, Sparwasser T. In vivo depletion of FoxP3+ Tregs using the DEREG mouse model. Methods Mol Biol. 2011;707:157-72. doi: 10.1007/978-1-61737-979-6_10.
77. Budhu S, Wolchok J, Merghoub T. The importance of animal models in tumor immunity and immunotherapy. Curr Opin Genet Dev. 2014;24:46-51. doi: 10.1016/j.gde.2013.11.008.
78. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134-44. doi: 10.1056/NEJMoa1305133.
79. McDermott DF, Sosman JA, Sznol M, Massard C, Gordon MS, Hamid O, et al. Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol. 2016;34(8):833-42. doi: 10.1200/jco.2015.63.7421.
80. Kohrt HE, Houot R, Goldstein MJ, Weiskopf K, Alizadeh AA, Brody J, et al. CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies. Blood. 2011;117(8):2423-32. doi: 10.1182/blood-2010-08-301945.
81. Kohrt HE, Houot R, Weiskopf K, Goldstein MJ, Scheeren F, Czerwinski D, et al. Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer. J Clin Invest. 2012;122(3):1066-75. doi: 10.1172/jci61226.
82. Curran MA, Kim M, Montalvo W, Al-Shamkhani A, Allison JP. Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production. PLoS One. 2011;6(4):e19499. doi: 10.1371/journal.pone.0019499.
83. Hurwitz AA, Foster BA, Kwon ED, Truong T, Choi EM, Greenberg NM, et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res. 2000;60(9):2444-8.
84. Selby M, Engelhardt J, Lu L-S, Quigley M, Wang C, Chen B et al. Antitumor activity of concurrent blockade of immune checkpoint molecules CTLA-4 and PD-1 in preclinical models. J Clin Oncol. 2013;31(2013 (suppl; abstr 3061)).
85. Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012;72(4):917-27. doi: 10.1158/0008-5472.can-11-1620.
86. Salcedo R, Hixon JA, Stauffer JK, Jalah R, Brooks AD, Khan T, et al. Immunologic and therapeutic synergy of IL-27 and IL-2: enhancement of T cell sensitization, tumor-specific CTL reactivity and complete regression of disseminated neuroblastoma metastases in the liver and bone marrow. J Immunol. 2009;182(7):4328-38. doi: 10.4049/jimmunol.0800471.
87. Murphy WJ, Welniak L, Back T, Hixon J, Subleski J, Seki N, et al. Synergistic anti-tumor responses after administration of agonistic antibodies to CD40 and IL-2: coordination of dendritic and CD8+ cell responses. J Immunol. 2003;170(5):2727-33.
88. Wigginton JM, Komschlies KL, Back TC, Franco JL, Brunda MJ, Wiltrout RH. Administration of interleukin 12 with pulse interleukin 2 and the rapid and complete eradication of murine renal carcinoma. J Natl Cancer Inst. 1996;88(1):38-43.
89. Guo Z, Wang X, Cheng D, Xia Z, Luan M, Zhang S. PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer. PLoS One. 2014;9(2):e89350. doi: 10.1371/journal.pone.0089350.
90. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122-33. doi: 10.1056/NEJMoa1302369.
91. Antonia SJ, Gettinger SN, Chow LQM, Juergens RA, Borghaei H, Shen Y et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in first-line NSCLC: Interim phase I results. J Clin Oncol. 2014;32(2014 (suppl; abstr 8023)).
92. Sampson JH, Vlahovic G, Sahebjam S, Omuro AMP, Baehring JM, Hafler DA et al. Preliminary safety and activity of nivolumab and its combination with ipilimumab in recurrent glioblastoma (GBM): CHECKMATE-143. J Clin Oncol. 2015;33(2015 (suppl; abstr 3010)).
93. Antonia S, Goldberg SB, Balmanoukian A, Chaft JE, Sanborn RE, Gupta A, et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016;17(3):299-308. doi: 10.1016/s1470-2045(15)00544-6.
94. Sznol M, Kluger HM, Callahan MK, Postow MA, Gordon RA, Segal NH, et al. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). J Clin Oncol. 2014;32:5s (2014 (suppl; abstr LBA9003)).
95. Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med. 2013;368(14):1365-6. doi: 10.1056/NEJMc1302338.
96. Amin A, Lawson DH, Salama AK, Koon HB, Guthrie TH, Thomas SS et al. A single-arm, open-label, phase II study to evaluate the safety of vemurafenib (VEM) followed by ipilimumab (IPI) in BRAF V600-mutated metastatic melanoma (MM). J Clin Oncol. 2015;33(2015 (suppl; abstr 9032)).
97. Rizvi N, Gettinger S, Goldman J, al.; e. Safety and efficacy of first-line nivolumab and ipilimumab in non-small cell lung cancer. 16th World Conference on Lung Cancer. Presented at: 16th World Conference on Lung Cancer. 2015;September 6-9(Denver, CO. Abstract 786.).
98. Bertrand A, Kostine M, Barnetche T, Truchetet ME, Schaeverbeke T. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med. 2015;13:211. doi: 10.1186/s12916-015-0455-8.
99. Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26(12):2375-91. doi: 10.1093/annonc/mdv383.
100. Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57-66. doi: 10.1016/s1470-2045(14)71170-2.
101. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509-18. doi: 10.1056/NEJMoa1215134.
102. Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics. 2016;3:16011. doi: 10.1038/mto.2016.11.
103. Bates SE, Berry DA, Balasubramaniam S, Bailey S, LoRusso PM, Rubin EH. Advancing clinical trials to streamline drug development. Clin Cancer Res. 2015;21(20):4527-35. doi: 10.1158/1078-0432.ccr-15-0039.
104. Emens LA, Butterfield LH, Hodi Jr FS, Marincola FM, Kaufman HL. Cancer immunotherapy trials: leading a paradigm shift in drug development. J Immunother Cancer. 2016;4:42. doi: 10.1186/s40425-016-0146-9.
105. Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412-20. doi: 10.1158/1078-0432.ccr-09-1624.
106. Hoos A, Eggermont AM, Janetzki S, Hodi FS, Ibrahim R, Anderson A, et al. Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst. 2010;102(18):1388-97. doi: 10.1093/jnci/djq310.
107. Wolchok J, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob J, Cowey C et al. Efficacy and safety results from a phase III trial of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naive patients (pts) with advanced melanoma (MEL) (CheckMate 067). 2015;33((suppl; abstr LBA1)).