Anti-programmed death-1 and anti-programmed death-ligand 1 antibodies in cancer therapy

Expert Opinion on Biological Therapy

Volumn 13, Issue 6, 2013, Pages 847-861

  Hamid, Omid ^a   Carvajal, Richard D ^b  

^a Angeles Clinic and Research Institute Melanoma Center   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Cancer; Immunotherapy; Nivolumab; Programmed death 1

Indexed keywords

AMP 224; ANTINEOPLASTIC AGENT; BEVACIZUMAB; BMS 936559; CANCER VACCINE; CORTICOSTEROID; CYCLOPHOSPHAMIDE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; INFLIXIMAB; IPILIMUMAB; MDX 1105; MEDI 4736; MK 3475; MONOCLONAL ANTIBODY; MPDL 3280A; NIVOLUMAB; OXALIPLATIN; PAZOPANIB; PIDILIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 MONOCLONAL ANTIBODY; PROGRAMMED DEATH LIGAND 1 MONOCLONAL ANTIBODY; RG 7446; RITUXIMAB; STEROID; SUNITINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VEMURAFENIB; ANTIBODY; CD274 PROTEIN, HUMAN; PDCD1 PROTEIN, HUMAN; PROGRAMMED DEATH 1 RECEPTOR;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; APPETITE; AREA UNDER THE CURVE; ARTHRALGIA; BREAST CANCER; CANCER IMMUNOTHERAPY; CANCER PROGNOSIS; CANCER REGRESSION; CANCER SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; COLITIS; COLORECTAL CANCER; COUGHING; CYTOKINE PRODUCTION; DIABETES MELLITUS; DIARRHEA; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ERUPTION; DRUG FEVER; DRUG MEGADOSE; DRUG SAFETY; ENDOPHTHALMITIS; FATIGUE; FOLLICULAR LYMPHOMA; FOLLOW UP; HEPATITIS; HODGKIN DISEASE; HUMAN; HYPOPHYSITIS; HYPOTHYROIDISM; IMMUNE RESPONSE; INFUSION RELATED REACTION; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MELANOMA; METASTASIS; METASTATIC COLORECTAL CANCER; METASTATIC MELANOMA; MULTIPLE CANCER; MULTIPLE MYELOMA; MYASTHENIA GRAVIS; MYELOID LEUKEMIA; NAUSEA; NONHODGKIN LYMPHOMA; OVARY CANCER; OVERALL SURVIVAL; PANCREAS CANCER; PNEUMONIA; PREDICTIVE VALUE; PROGRESSION FREE SURVIVAL; PROSTATE CANCER; PROTEIN EXPRESSION; PRURITUS; REVIEW; SARCOIDOSIS; SIDE EFFECT; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; SOLID TUMOR; STOMACH CANCER; T LYMPHOCYTE ACTIVATION; THYROIDITIS; UNSPECIFIED SIDE EFFECT; VITILIGO; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; IMMUNOLOGY; METABOLISM; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PATHOLOGY; TUMOR ESCAPE;

ANIMALS; ANTIBODIES; ANTIGENS, CD274; ANTINEOPLASTIC AGENTS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; SIGNAL TRANSDUCTION; TUMOR ESCAPE;

EID: 84877882244     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.2013.770836     Document Type: Review

References (120)

1. Parish CR. Cancer immunotherapy: The past, the present and the future. Immunol Cell Biol 2003;81(2):106-13
2. Kirkwood JM, Butterfield LH, Tarhini AA, et al. Immunotherapy of cancer in 2012. CA Cancer J Clin 2012; [Epub ahead of print]
3. Sherwin SA, Knost JA, Fein S, et al. A multiple-dose phase I trial of recombinant leukocyte A interferon in cancer patients. JAMA 1982;248(19):2461-6
4. Kirkwood JM, Ernstoff MS. Interferons in the treatment of human cancer. J Clin Oncol 1984;2(4):336-52
5. Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 1985;313(23):1485-92
6. Rosenberg SA, Lotze MT, Yang JC, et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 1993;21:85:622-32
7. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; [Epub ahead of print]
8. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455-65
9. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 1992;11:3887-95
10. Liang SC, Latchman YE, Buhlmann JE, et al. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol 2003;33:2706-16
11. Probst HC, McCoy K, Okazaki T, et al. Resting dendritic cells induce peripheral CD8+ T-cell tolerance through PD-1 and CTLA-4. Nat Immunol 2005;6:280-6
12. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008;26:677-704
13. Dong H, Strome SE, Matteson EL, et al. 2003;Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. J Clin Invest 2003;111:363-70
14. Okazaki T, Honjo T. PD-1 and PD-1 ligands: From discovery to clinical application. Int Immunol 2007;19:813-24
15. Iwai Y, Terawaki S, Ikegawa M, et al. PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med 2003;198:39-50
16. Nishimura H, Agata Y, Kawasaki A, et al. Developmentally regulated expression of the PD-1 protein on the surface of double-negative (CD4-CD8-) thymocytes. Int Immunol 1996;8:773-80
17. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, costimulates T-cell proliferation and interleukin-10 secretion. Nat Med 1999;5:1365-9
18. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000;192:1027-34
19. Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2001;2:261-8
20. Tseng SY, Otsuji M, Gorski K, et al. B7- DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med 2001;193:839-46
21. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 2008;8(6):467-77
22. Chapoval AI, Ni J, Lau JS, et al. B7-H3: A costimulatory molecule for T-cell activation and IFN-gamma production. Nat Immunol 2001;2(3):269-74
23. Linsley PS, Greene JL, Brady W, et al. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1994;1:793-801
24. Teft WA, Kirchhof MG, Madrenas J. A molecular perspective of CTLA-4 function. Annu Rev Immunol 2006;24:65-97
25. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995;182(2):459-65
26. Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol 2005;25(21):9543-53
27. Topalian SL, Drake CG, Pardoll DM. Targeting t e PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012;24(2):207-12
28. Fallarino F, Grohmann U, Hwang KW, et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 2003;4:1206-12
29. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006;6:295-307
30. Ueda H, Howson JM, Esposito L, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003;423:506-11
31. Topalian SL, Weiner GJ, Pardoll DM. Cancer i munotherapy comes of age. J Clin Oncol 2011;29(36):4828-36
32. Tivol EA, Borriello F, Schweitzer AN, et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995;3:541-7
33. Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science 1995;270:985-8
34. Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999;11:141-51
35. Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptordeficient mice. Science 2001;291:319-22
36. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med 2002;8:793-800
37. Eppihimer MJ, Gunn J, Freeman GJ, et al. Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation 2002;9:133-45
38. Curiel TJ, Wei S, Dong H, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003;9:562-7
39. Loke P, Allison JP. PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells. Proc Natl Acad Sci USA 2003;100:5336-41
40. Kryczek I, Wei S, Gong W, et al. Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development. J Immunol 2008;181(9):5842-6
41. Wilke CM, Wei S, Wang L, et al. Dual biological effects of the cytokines interleukin-10 and interferon-gamma. Cancer Immunol Immunother 2011;60:1529-41
42. Jiang X, Zhou J, Giobbie-Hurder A, et al. The paradoxical activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin Cancer Res 2013;19(3):598-609
43. Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 2012;4(127):127ra37
44. Butte MJ, Keir ME, Phamduy TB, et al. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 2007;27:111-22
45. Bennett F, Luxenberg D, Ling V, et al. Program death-1 engagement upon TCR activation has distinct effects on costimulation and cytokine-driven proliferation: Attenuation of ICOS, IL-4, and IL-21, but not CD28, IL-7, and IL-15 responses. J Immunol 2003;170:711-18
46. Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 2003;170:1257-66
47. Rodig N, Ryan T, Allen JA, et al. Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis. Eur J Immunol 2003;33:3117-26
48. Tsuda M, Matsumoto K, Inoue H, et al. Expression of B7-H1 and B7-DC on the airway epithelium is enhanced by double-stranded RNA. Biochem Biophys Res Commun 2005;330:263-70
49. Mataki N, Kikuchi K, Kawai T, et al. Expression of PD-1, PD-L1, and PD-L2 in the liver in autoimmune liver diseases. Am J Gastroenterol 2007;102:302-12
50. Rozali EN, Hato SV, Robinson BW, et al. Programmed death ligand 2 in cancer-induced immune suppression. Clin Dev Immunol 2012;656340
51. Messal N, Serriari NE, Pastor S, et al. PD-L2 is expressed on activated human T cells and regulates their function. Mol Immunol 2011;48(15-16):2214-19
52. De Monte L, Reni M, Tassi E, et al.Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med 2011;208(3):469-78
53. Nguyen LT, Radhakrishnan S, Ciric B, et al. Cross-linking the B7 family molecule B7-DC directly activates immune functions of dendritic cells. J Exp Med 2002;196:1393-8
54. Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent antiprogrammed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28(19):3167-75
55. Youngnak P, Kozono Y, Kozono H, et al. Differential binding properties of B7-H1 and B7-DC to programmed death-1. Biochem Biophys Res Commun 2003;307(3):672-7
56. Ohigashi Y, Sho M, Yamada Y, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 2005;11(8):2947-53
57. Nomi T, Sho M, Akahori T, et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 2007;13(7):2151-7
58. Hamanishi J, Mandai M, Iwasaki M, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci USA 2007;104(9):3360-5
59. Rosenwald A, Wright G, Leroy K, et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003;198(6):851-62
60. Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 2010;116(17):3268-77
61. Nazareth MR, Broderick L, Simpson-Abelson MR, e al. Characterization of human lung tumor-associated fibroblasts and their ability to modulate the activation of tumor-associated T cells. J Immunol 2007;178(9):5552-62
62. Leach DR, Krummel MF, Allison JP. Enhancement o antitumor immunity by CTLA-4 blockade. Science 1996;271(5256):1734-6
63. Kwon ED, Hurwitz AA, Foster BA, et al. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci USA 1997;94(15):8099-103
64. Yang YF, Zou JP, Mu J, et al. Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: The effect is manifested only at the restricted tumor-bearing stages. Cancer Res 1997;57(18):4036-41
65. Kwon ED, Foster BA, Hurwitz AA, et al. Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA- 4) blockade immunotherapy. Proc Natl Acad Sci USA 1999;96(26):15074-9
66. Korman A, Yellin M, Keler T. Tumor immunotherapy: Preclinical and clinical activity of anti-CTLA4 antibodies. Curr Opin Investig Drugs 2005;6:582-91
67. Hurwitz AA, Foster BA, Kwon ED, et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res 2000;60(9):2444-8
68. Tchekmedyian S, Glasby J, Korman A, et al. MDX-010 (human anti-CTLA4): A phase I trial in malignant melanoma. J Clin Oncol 2002;21:abstract 56
69. Davis TA, Tchekmedyian S, Korman A, et al. MDX-010 (human anti-CTLA4): A phase 1 trial in hormone refractory prostate carcinoma (HRPC). Proc Am Soc Clin Oncol 2002;21:abstract 74
70. Hodi FS, Mihm MC, Soiffer RJ, et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA 2003;100:4712-17
71. Ribas A, Camacho LH, Lopez-Berestein G, et al. 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. J Clin Oncol 2005;23:8968-77
72. Gomez-Navarro J, Sharma A, Bozon V, et al. Dose and schedule selection for the anti-CTLA-4 monoclonal antibody CP-675,206 in patients (pts) with metastatic melanoma [abstract 8032]. J Clin Oncol 2006;24(18 Suppl):s460
73. O'Day SJ, Hamid O, Urba WJ. Targeting c totoxic T-lymphocyte antigen-4 (CTLA-4): A novel strategy for the treatment of melanoma and other malignancies. Cancer 2007;110:2614-27
74. Hamid O, Urba W, Yellin M, et al. Kinetics of response to ipilimumab (MDX-010) in patients with stage III/IV melanoma. J Clin Oncol 2007;25(18 Suppl):abstract 8525
75. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23
76. Chemnitz JM, Eggle D, Driesen J, et al. RNA fingerprints provide direct evidence for the inhibitory role of TGF beta and PD-1 on CD4+ Tcells in Hodgkin lymphoma. Blood 2007;110(9):3226-33
77. Ahmadzadeh M, Johnson LA, Heemskerk B, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 2009;114:1537-44
78. Zhang Y, Huang S, Gong D, et al. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol 2010;7:389-95
79. Chapon M, Randriamampita C, Maubec E, et al. Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes. J Invest Dermatol 2011;131:1300-7
80. Thompson RH, Dong H, Lohse CM, et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res 2007;13:1757-61
81. Shi F, Shi M, Zeng Z, et al. PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer 2010; [Epub ahead of print]
82. Hino R, Kabashima K, Kato Y, et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 2010;116(7):1757-66
83. Mu CY, Huang JA, Chen Y, et al. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol 2010; [Epub ahead of print]
84. Gao Q, Wang XY, Qiu SJ, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res 2009;15:971-9
85. Files DB, Sandler BJ, Sznol M, Chen L. Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy. Yale J Biol Med 2011;84(4):409-21
86. Wong RM, Scotland RR, Lau RL, et al. Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int Immunol 2007;19:1223-34
87. Wang W, Lau R, Yu D, et al. PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells. Int Immunol 2009;21(9):1065-77
88. Li B, VanRoey M, Wang C, et al. Anti-programmed death-1 synergizes with granulocyte macrophage colony-stimulating factor-secreting tumor cell immunotherapy providing therapeutic benefit to mice with established tumors. Clin Cancer Res 2009;15(5):1623-34
89. Mangsbo SM, Sandin LC, et al. Enhanced t mor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy. J Immunother 2010;33(3):225-35
90. Woo SR, Turnis ME, Goldberg MV, 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
91. Benson DM Jr, Bakan CE, Mishra A, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: A therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood 2010;116:2286-94
92. Rosenblatt J, Glotzbecker B, Mills H, et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother 2011;34(5):409-18
93. Mkrtichyan M, Najjar YG, Raulfs EC, et al. Anti-PD-1 synergizes with cyclophosphamide to induce potent anti-tumor vaccine effects through novel mechanisms. Eur J Immunol 2011;41(10):2977-86
94. Beck A, Wurch T, Reichert J. 6th Annual European Antibody Congress 2010. Meeting report. November 29-December 1 2010; Geneva, Switzerland. Published online 2011 March 1 MAbs 2011;3(2):111-32
95. GlaxoSmithKline and Amplimmune Form Global Strategic Collaboration. Available from: Http://www.prnewswire. com/news-releases/glaxosmithkline- andamplimmune- form-global-strategiccollaboration- 99938599.html [Last accessed 3 August 2012]
96. Mkrtichyan M, Najjar YG, Raulfs EC, et al. B7-DC-Ig enhances vaccine effect by a novel mechanism dependent on PD-1 expression level on T cell subsets. J Immunol 2012;189(5):2338-47
97. Topalian SL, Brahmer JR, Hodi FS, et al. Anti-PD-1 (BMS-936558/MDX- 1106/ONO-4538) in patients with advanced solid tumors: Clinical activity, safety, and molecular markers. Poster presentation European Society for Medical Oncology; 2012
98. Wolchok JD, Hoos A, O'Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: Immune-related response criteria. Clin Cancer Res 2009;15:7412-20
99. Agrawal S, Feng Y, Kollia G, et al. Clinical pharmacokinetics (PK) of BMS-936558, a fully human anti-PD-1 monoclonal antibody. J Clin Oncol 2012;30(Suppl): Abstract TPS2622-poster presented at ASCO 2012. Chicago, Illinois, USA. 4 June 2012
100. Berger R, Rotem-Yehudar R, Slama G, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res 2008;14:3044-51
101. Rotem-Yehudar R, Armand P, Devine S, et al. The humanized anti PD-1 antibody, CT-011, increases specific CD4+ effector/memory and memory T lymphocytes in patients with diffuse large B cell lymphoma (DLBCL) following autologous stem cell transplantation (AuSCT). Blood (ASH Annual Meeting Abstracts) 2009. 114: Abstract 1216
102. Westin JR, Chu F, Fayad LE, et al.Phase II safety and efficacy study of CT-011, a humanized anti-PD-1 monoclonal antibody, in combination with rituximab in patients with relapsed follicular lymphoma. Oral presentation presented on December 10, 2012. ASH 2012; Atlanta, Georgia, USA; 2012
103. Patnaik A, Kang SP, Tolcher AW, et al.Phase I study of MK-3475 (anti-PD- 1 monoclonal antibody) in patients with advanced solid tumors. Presented 2 June 2012 at ASCO 2012; Chicago, Illinois, USA; 2012
104. Hamid O, Daud A, Robert C, et al.Preliminary Clinical Efficacy and Safety of MK-3475 (Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Melanoma. Presented at Society for Melanoma Research 2012; Hollywood, California, USA; 2012
105. Ku GY, Yuan J, Page DB, et al.Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: Lymphocyte count after 2 doses correlates with survival. Cancer 2010;116(7):1767-75
106. Hamid O, Schmidt H, Nissan A, et al. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J Transl Med 2011;9:204
107. Postow MA, Yuan J, Panageas K, et al.Evaluation of the absolute lymphocyte count as a biomarker for melanoma patients treated with the commercially available dose of ipilimumab (3mg/kg). J Clin Oncol 2012;30(Suppl): Abstract 8575
108. Woo SR, Turnis ME, Goldberg MV, 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
109. Sakuishi K, Apetoh L, Sullivan JM, et al.Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 2010;207(10):2187-94
110. Melero I, Hervas-Stubbs S, Glennie M, et al. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer 2007;7(2):95-106
111. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature 2011;480(7378):480-9
112. Pardoll D, Drake C. Immunotherapy earns its spot in the ranks of cancer therapy. J Exp Med 2012;209(2):201-9
113. Menetrier-Caux C, Curiel T, Faget J, et al. Targeting regulatory T cells. Target Oncol 2012;7(1):15-28
114. Karim R, Jordanova ES, Piersma SJ, et al. Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma. Clin Cancer Res 2009;15:6341-7
115. Grimm M, Gasser M, Koenigshausen M. Clinical significance and therapeutic potential of programmed death-1 ligand- 1 and programmed death-1 ligand- 2 expression in human colorectal cancer. J Clin Oncol 2008;26(Suppl): Abstract 15005
116. Wu C, Zhu Y, Jiang J, et al.Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem 2006;108:19-24
117. Zeng Z, Shi F, Zhou L, et al.Upregulation of circulating PD-L1/PD- 1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma. PLoS One 2011;6(9):e23621
118. Hamanishi J, Mandai M, Abiko K, et al.The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors. Clin Immunol 2011;141:338-47
119. Thompson RH, Kuntz SM, Leibovich BC, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 2006;66:3381-5
120. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med 2012;366(26):2517-19