Therapeutic targets and new directions for antibodies developed for ovarian cancer

mAbs

Volumn 8, Issue 8, 2016, Pages 1437-1455

  Bax, Heather J ^a   Josephs, Debra H ^a   Pellizzari, Giulia ^a   Spicer, James F ^a   Montes, Ana ^b   Karagiannis, Sophia N ^a  

^a GUY S HOSPITAL   (United Kingdom)

^b GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Antibodies; clinical trials; immune checkpoint; immunotherapy; molecular targeting; ovarian cancer; tumor associated antigen; tumor promoting molecule; vaccine

Indexed keywords

ABAGOVOMAB; AMATUXIMAB; AVELUMAB; BEVACIZUMAB; CA 125 ANTIGEN; CATUMAXOMAB; CETUXIMAB; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; EPHRIN RECEPTOR A4; EPIDERMAL GROWTH FACTOR RECEPTOR; EPITHELIAL CELL ADHESION MOLECULE; FARLETUZUMAB; FOLATE RECEPTOR 1; IMALUMAB; INTERLEUKIN 6; MACROPHAGE MIGRATION INHIBITION FACTOR; MATUZUMAB; MESOTHELIN; MUCIN 1; OLARATUMAB; PANITUMUMAB; PERTUZUMAB; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PROGRAMMED DEATH 1 RECEPTOR; SERIBANTUMAB; SILTUXIMAB; SODIUM PHOSPHATE COTRANSPORTER 2B; TRASTUZUMAB; UNINDEXED DRUG; VASCULOTROPIN RECEPTOR; ANTIBODY;

APOPTOSIS; CELL INVASION; CELL MIGRATION; DRUG EFFICACY; DRUG SAFETY; HUMAN; NATURAL KILLER CELL; OVARY CANCER; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SURVIVAL RATE; FEMALE; IMMUNOLOGY; OVARY TUMOR; PASSIVE IMMUNIZATION; PROCEDURES;

ANTIBODIES; FEMALE; HUMANS; IMMUNIZATION, PASSIVE; OVARIAN NEOPLASMS;

EID: 84992745494     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.1080/19420862.2016.1219005     Document Type: Review

References (163)

1. S.Statistics. http://seer.cancer.gov/statfacts/html/ovary.html. 2016.
2. L.Huang, K.A.Cronin, K.A.Johnson, A.B.Mariotto, E.J.Feuer. Improved survival time:what can survival cure models tell us about population-based survival improvements in late-stage colorectal, ovarian, and testicular cancer? Cancer 2008; 112:2289-300; PMID:18393325; http://dx.doi.org/10.1002/cncr.23425
3. L.Zhang, J.R.Conejo-Garcia, D.Katsaros, P.A.Gimotty, M.Massobrio, G.Regnani, A.Makrigiannakis, H.Gray, K.Schlienger, M.N.Liebman, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348:203-13; PMID:12529460; http://dx.doi.org/10.1056/NEJMoa020177
4. M.S.Patankar, Y.Jing, J.C.Morrison, J.A.Belisle, F.A.Lattanzio, Y.Deng, N.K.Wong, H.R.Morris, A.Dell, G.F.Clark. Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125. Gynecol Oncol 2005; 99:704-13; PMID:16126266; http://dx.doi.org/10.1016/j.ygyno.2005.07.030
5. J.A.Gubbels, M.Felder, S.Horibata, J.A.Belisle, A.Kapur, H.Holden, S.Petrie, M.Migneault, C.Rancourt, J.P.Connor, et al. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells. Mol Cancer 2010; 9:11; PMID:20089172; http://dx.doi.org/10.1186/1476-4598-9-11
6. H.Bouanene, A.Miled. Conflicting views on the molecular structure of the cancer antigen CA125/MUC16. Dis Markers 2010; 28:385-94; PMID:20683153; http://dx.doi.org/10.1155/2010/918457
7. J.A.Gubbels, J.Belisle, M.Onda, C.Rancourt, M.Migneault, M.Ho, T.K.Bera, J.Connor, B.K.Sathyanarayana, B.Lee, et al. Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. Mol Cancer 2006; 5:50; PMID:17067392; http://dx.doi.org/10.1186/1476-4598-5-50
8. G.J.Rustin, M.Marples, A.E.Nelstrop, M.Mahmoudi, T.Meyer. Use of CA-125 to define progression of ovarian cancer in patients with persistently elevated levels. J Clin Oncol 2001; 19:4054-7; PMID:11600607
9. J.Deng, L.Wang, H.Chen, L.Li, Y.Ma, J.Ni, Y.Li. The role of tumour-associated MUC1 in epithelial ovarian cancer metastasis and progression. Cancer Metastasis Rev 2013; 32:535-51; PMID:23609751; http://dx.doi.org/10.1007/s10555-013-9423-y
10. J.Wesseling, S.W.van der Valk, H.L.Vos, A.Sonnenberg, J.Hilkens. Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J Cell Biol 1995; 129:255-65; PMID:7698991; http://dx.doi.org/10.1083/jcb.129.1.255
11. A.Rughetti, V.Turchi, C.A.Ghetti, G.Scambia, P.B.Panici, G.Roncucci, S.Mancuso, L.Frati, M.Nuti. Human B-cell immune response to the polymorphic epithelial mucin. Cancer Res 1993; 53:2457-9; PMID:8495404
12. A.L.Oei, M.Moreno, R.H.Verheijen, F.C.Sweep, C.M.Thomas, L.F.Massuger, S.von Mensdorff-Pouilly. Induction of IgG antibodies to MUC1 and survival in patients with epithelial ovarian cancer. Int J Cancer 2008; 123:1848-53; PMID:18661524; http://dx.doi.org/10.1002/ijc.23725
13. S.Bellone, E.R.Siegel, E.Cocco, M.Cargnelutti, D.A.Silasi, M.Azodi, P.E.Schwartz, T.J.Rutherford, S.Pecorelli, A.D.Santin. Overexpression of epithelial cell adhesion molecule in primary, metastatic, and recurrent/chemotherapy-resistant epithelial ovarian cancer:implications for epithelial cell adhesion molecule-specific immunotherapy. Int J Gynecol Cancer 2009; 19:860-6; PMID:19574774; http://dx.doi.org/10.1111/IGC.0b013e3181a8331f
14. G.Spizzo, P.Went, S.Dirnhofer, P.Obrist, H.Moch, P.A.Baeuerle, E.Mueller-Holzner, C.Marth, G.Gastl, A.G.Zeimet. Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer. Gynecol Oncol 2006; 103:483-8; PMID:16678891; http://dx.doi.org/10.1016/j.ygyno.2006.03.035
15. B.T.van der Gun, L.J.Melchers, M.H.Ruiters, L.F.de Leij, P.M.McLaughlin, M.G.Rots. EpCAM in carcinogenesis:the good, the bad or the ugly. Carcinogenesis 2010; 31:1913-21; PMID:20837599; http://dx.doi.org/10.1093/carcin/bgq187
16. N.Parker, M.J.Turk, E.Westrick, J.D.Lewis, P.S.Low, C.P.Leamon. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem 2005; 338:284-93; PMID:15745749; http://dx.doi.org/10.1016/j.ab.2004.12.026
17. M.K.Siu, D.S.Kong, H.Y.Chan, E.S.Wong, P.P.Ip, L.Jiang, H.Y.Ngan, X.F.Le, A.N.Cheung. Paradoxical impact of two folate receptors, FRalpha and RFC, in ovarian cancer:effect on cell proliferation, invasion and clinical outcome. PLoS One 2012; 7:e47201; PMID:23144806; http://dx.doi.org/10.1371/journal.pone.0047201
18. K.R.Kalli, A.L.Oberg, G.L.Keeney, T.J.Christianson, P.S.Low, K.L.Knutson, L.C.Hartmann. Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecol Oncol 2008; 108:619-26; PMID:18222534; http://dx.doi.org/10.1016/j.ygyno.2007.11.020
19. Y.L.Chen, M.C.Chang, C.Y.Huang, Y.C.Chiang, H.W.Lin, C.A.Chen, C.Y.Hsieh, W.F.Cheng. Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response. Mol Oncol 2012; 6:360-9; PMID:22265591; http://dx.doi.org/10.1016/j.molonc.2011.11.010
20. I.B.Vergote, C.Marth, R.L.Coleman. Role of the folate receptor in ovarian cancer treatment:evidence, mechanism, and clinical implications. Cancer Metastasis Rev 2015; 34:41-52; PMID:25564455; http://dx.doi.org/10.1007/s10555-014-9539-8
21. J.I.Coward, K.Middleton, F.Murphy. New perspectives on targeted therapy in ovarian cancer. Int J Womens Health 2015; 7:189-203; PMID:25678824; http://dx.doi.org/10.2147/IJWH.S52379
22. A.Cerezo, M.C.Guadamillas, J.G.Goetz, S.Sanchez-Perales, E.Klein, R.K.Assoian, M.A.del Pozo. The absence of caveolin-1 increases proliferation and anchorage- independent growth by a Rac-dependent, Erk-independent mechanism. Mol Cell Biol 2009; 29:5046-59; PMID:19620284; http://dx.doi.org/10.1128/MCB.00315-09
23. A.Cheung, H.J.Bax, D.H.Josephs, K.M.Ilieva, G.Pellizzari, J.Opzoomer, J.Bloomfield, M.Fittall, A.Grigoriadis, M.Figini, et al. Targeting folate receptor alpha for cancer treatment. Oncotarget 2016; PMID:27248175; http://dx.doi.org/10.18632/oncotarget.9651
24. M.R.Buist, C.F.Molthoff, P.Kenemans, C.J.Meijer. Distribution of OV-TL 3 and MOv18 in normal and malignant ovarian tissue. J Clin Pathol 1995; 48:631-6; PMID:7560169; http://dx.doi.org/10.1136/jcp.48.7.631
25. K.L.Knutson, C.J.Krco, C.L.Erskine, K.Goodman, L.E.Kelemen, P.J.Wettstein, P.S.Low, L.C.Hartmann, K.R.Kalli. T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer. J Clin Oncol 2006; 24:4254-61; PMID:16908932; http://dx.doi.org/10.1200/JCO.2006.05.9311
26. I.Pastan, R.Hassan. Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res 2014; 74:2907-12; PMID:24824231; http://dx.doi.org/10.1158/0008-5472.CAN-14-0337
27. K.M.Burleson, R.C.Casey, K.M.Skubitz, S.E.Pambuccian, T.R.Oegema, Jr., A.P.Skubitz. Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol 2004; 93:170-81; PMID:15047232; http://dx.doi.org/10.1016/j.ygyno.2003.12.034
28. W.F.Cheng, C.Y.Huang, M.C.Chang, Y.H.Hu, Y.C.Chiang, Y.L.Chen, C.Y.Hsieh, C.A.Chen. High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma. Br J Cancer 2009; 100:1144-53; PMID:19293794; http://dx.doi.org/10.1038/sj.bjc.6604964
29. L.G.Hudson, R.Zeineldin, M.Silberberg, M.S.Stack. Activated epidermal growth factor receptor in ovarian cancer. Cancer Treat Res 2009; 149:203-26; PMID:19763438; http://dx.doi.org/10.1007/978-0-387-98094-2_10
30. I.Dimova, B.Zaharieva, S.Raitcheva, R.Dimitrov, N.Doganov, D.Toncheva. Tissue microarray analysis of EGFR and erbB2 copy number changes in ovarian tumors. Int J Gynecol Cancer 2006; 16:145-51; PMID:16445625; http://dx.doi.org/10.1111/j.1525-1438.2006.00286.x
31. A.Casamassimi, A.De Luca, S.Agrawal, K.Stromberg, D.S.Salomon, N.Normanno. EGF-related antisense oligonucleotides inhibit the proliferation of human ovarian carcinoma cells. Ann Oncol 2000; 11:319-25; PMID:10811499; http://dx.doi.org/10.1023/A:1008350811639
32. H.Kurachi, K.Morishige, H.Adachi, K.Adachi, K.Tasaka, M.Sawada, A.Miyake. Implantation and growth of epidermal growth factor (EGF) receptor expressing human ovarian cancer xenografts in nude mice is dependent on EGF. Cancer 1994; 74:2984-90; PMID:7954262; http://dx.doi.org/10.1002/1097-0142(19941201)74:11%3c2984::AID-CNCR2820741115%3e3.0.CO;2-M
33. O.Alper, E.S.Bergmann-Leitner, T.A.Bennett, N.F.Hacker, K.Stromberg, W.G.Stetler-Stevenson. Epidermal growth factor receptor signaling and the invasive phenotype of ovarian carcinoma cells. J Natl Cancer Inst 2001; 93:1375-84; PMID:11562388; http://dx.doi.org/10.1093/jnci/93.18.1375
34. O.Alper, M.L.De Santis, K.Stromberg, N.F.Hacker, Y.S.Cho-Chung, D.S.Salomon. Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells. Int J Cancer 2000; 88:566-74; PMID:11058872; http://dx.doi.org/10.1002/1097-0215(20001115)88:4%3c566::AID-IJC8%3e3.0.CO;2-D
35. X.H.Peng, P.Karna, Z.Cao, B.H.Jiang, M.Zhou, L.Yang. Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem 2006; 281:25903-14; PMID:16847054; http://dx.doi.org/10.1074/jbc.M603414200
36. F.Wang, R.Liu, S.W.Lee, C.M.Sloss, J.Couget, J.C.Cusack. Heparin-binding EGF-like growth factor is an early response gene to chemotherapy and contributes to chemotherapy resistance. Oncogene 2007; 26:2006-16; PMID:17001310; http://dx.doi.org/10.1038/sj.onc.1209999
37. J.Anticancer researchAm, A.Pathol Psyrri, M.Kassar, Z.Yu, A.Bamias, P.M.Weinberger, S.Markakis, D.Kowalski, R.L.Camp, D.L.Rimm, M.A.Dimopoulos. Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer. Clin Cancer Res 2005; 11:8637-43; PMID:16361548; http://dx.doi.org/10.1158/1078-0432.CCR-05-1436
38. G.D.Shah, N.Loizos, H.Youssoufian, J.D.Schwartz, E.K.Rowinsky. Rationale for the development of IMC-3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet-derived growth factor receptor alpha. Cancer 2010; 116:1018-26; PMID:20127943; http://dx.doi.org/10.1002/cncr.24788
39. R.Henriksen, K.Funa, E.Wilander, T.Backstrom, M.Ridderheim, K.Oberg. Expression and prognostic significance of platelet-derived growth factor and its receptors in epithelial ovarian neoplasms. Cancer Res 1993; 53:4550-4; PMID:8402626
40. C.V.Madsen, K.Dahl Steffensen, M.Waldstrom, A.Jakobsen. Immunohistochemical expression of platelet-derived growth factor receptors in ovarian cancer patients with long-term follow-up. Patholog Res Int 2012; 2012:851432; PMID:23094199; http://dx.doi.org/10.1155/2012/851432
41. D.Matei, R.E.Emerson, Y.C.Lai, L.A.Baldridge, J.Rao, C.Yiannoutsos, D.D.Donner. Autocrine activation of PDGFRalpha promotes the progression of ovarian cancer. Oncogene 2006; 25:2060-9; PMID:16331269; http://dx.doi.org/10.1038/sj.onc.1209232
42. V.Gryshkova, I.Goncharuk, V.Gurtovyy, Y.Khozhayenko, S.Nespryadko, L.Vorobjova, V.Usenko, I.Gout, V.Filonenko, R.Kiyamova. The study of phosphate transporter NAPI2B expression in different histological types of epithelial ovarian cancer. Exp Oncol 2009; 31:37-42; PMID:19300415
43. M.Damelin, A.Bankovich, A.Park, J.Aguilar, W.Anderson, M.Santaguida, M.Aujay, S.Fong, K.Khandke, V.Pulito, et al. Anti-EFNA4 calicheamicin conjugates effectively target triple-negative breast and ovarian tumor-initiating cells to result in sustained tumor regressions. Clin Cancer Res 2015; 21:4165-73; PMID:26015513; http://dx.doi.org/10.1158/1078-0432.CCR-15-0695
44. L.M.Ellis, D.J.Hicklin. VEGF-targeted therapy:mechanisms of anti-tumour activity. Nat Rev Cancer 2008; 8:579-91; PMID:18596824; http://dx.doi.org/10.1038/nrc2403
45. I.Sher, S.A.Adham, J.Petrik, B.L.Coomber. Autocrine VEGF-A/KDR loop protects epithelial ovarian carcinoma cells from anoikis. Int J Cancer 2009; 124:553-61; PMID:19004006; http://dx.doi.org/10.1002/ijc.23963
46. D.I.Gabrilovich, H.L.Chen, K.R.Girgis, H.T.Cunningham, G.M.Meny, S.Nadaf, D.Kavanaugh, D.P.Carbone. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 1996; 2:1096-103; PMID:8837607; http://dx.doi.org/10.1038/nm1096-1096
47. R.N.Kaplan, R.D.Riba, S.Zacharoulis, A.H.Bramley, L.Vincent, C.Costa, D.D.MacDonald, D.K.Jin, K.Shido, S.A.Kerns, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005; 438:820-7; PMID:16341007; http://dx.doi.org/10.1038/nature04186
48. S.K.Kassim, E.M.El-Salahy, S.T.Fayed, S.A.Helal, T.Helal, D.Azzam Eel, A.Khalifa. Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients. Clin Biochem 2004; 37:363-9; PMID:15087251; http://dx.doi.org/10.1016/j.clinbiochem.2004.01.014
49. L.Li, L.Wang, W.Zhang, B.Tang, J.Zhang, H.Song, D.Yao, Y.Tang, X.Chen, Z.Yang, et al. Correlation of serum VEGF levels with clinical stage, therapy efficacy, tumor metastasis and patient survival in ovarian cancer. Anticancer Res 2004; 24:1973-9; PMID:15274387
50. L.A.Hefler, R.Zeillinger, C.Grimm, A.K.Sood, W.F.Cheng, A.Gadducci, C.B.Tempfer, A.Reinthaller. Preoperative serum vascular endothelial growth factor as a prognostic parameter in ovarian cancer. Gynecol Oncol 2006; 103:512-7; PMID:16750560; http://dx.doi.org/10.1016/j.ygyno.2006.03.058
51. E.Bandiera, R.Franceschini, C.Specchia, E.Bignotti, C.Trevisiol, M.Gion, S.Pecorelli, A.D.Santin, A.Ravaggi. Prognostic significance of vascular endothelial growth factor serum determination in women with ovarian cancer. ISRN Obstet Gynecol 2012; 2012:245756; PMID:22792477; http://dx.doi.org/10.5402/2012/245756
52. A.Rabinovich, L.Medina, B.Piura, S.Segal, M.Huleihel. Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6. Anticancer Res 2007; 27:267-72; PMID:17352242
53. G.Scambia, U.Testa, P.Benedetti Panici, E.Foti, R.Martucci, A.Gadducci, A.Perillo, V.Facchini, C.Peschle, S.Mancuso. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br J Cancer 1995; 71:354-6; PMID:7841052; http://dx.doi.org/10.1038/bjc.1995.71
54. R.T.Penson, K.Kronish, Z.Duan, A.J.Feller, P.Stark, S.E.Cook, L.R.Duska, A.F.Fuller, A.K.Goodman, N.Nikrui, et al. Cytokines IL-1beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFalpha in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel. Int J Gynecol Cancer 2000; 10:33-41; PMID:11240649; http://dx.doi.org/10.1046/j.1525-1438.2000.00003.x
55. J.M.Watson, J.S.Berek, O.Martinez-Maza. Growth inhibition of ovarian cancer cells induced by antisense IL-6 oligonucleotides. Gynecol Oncol 1993; 49:8-15; PMID:8482564; http://dx.doi.org/10.1006/gyno.1993.1077
56. N.H.Obata, K.Tamakoshi, K.Shibata, F.Kikkawa, Y.Tomoda. Effects of interleukin-6 on in vitro cell attachment, migration and invasion of human ovarian carcinoma. Anticancer Res 1997; 17:337-42; PMID:9066674
57. M.B.Nilsson, R.R.Langley, I.J.Fidler. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 2005; 65:10794-800; PMID:16322225; http://dx.doi.org/10.1158/0008-5472.CAN-05-0623
58. T.Hirano, K.Nakajima, M.Hibi. Signaling mechanisms through gp130:a model of the cytokine system. Cytokine Growth Factor Rev 1997; 8:241-52; PMID:9620640; http://dx.doi.org/10.1016/S1359-6101(98)80005-1
59. Y.Wang, X.L.Niu, Y.Qu, J.Wu, Y.Q.Zhu, W.J.Sun, L.Z.Li. Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Lett 2010; 295:110-23; PMID:20236757; http://dx.doi.org/10.1016/j.canlet.2010.02.019
60. T.Ohta, M.Ohmichi, T.Hayasaka, S.Mabuchi, M.Saitoh, J.Kawagoe, K.Takahashi, H.Igarashi, B.Du, M.Doshida, et al. Inhibition of phosphatidylinositol 3-kinase increases efficacy of cisplatin in in vivo ovarian cancer models. Endocrinology 2006; 147:1761-9; PMID:16396982; http://dx.doi.org/10.1210/en.2005-1450
61. M.Krockenberger, Y.Dombrowski, C.Weidler, M.Ossadnik, A.Honig, S.Hausler, H.Voigt, J.C.Becker, L.Leng, A.Steinle, et al. Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D. J Immunol 2008; 180:7338-48; PMID:18490733; http://dx.doi.org/10.4049/jimmunol.180.11.7338
62. M.Krockenberger, P.Kranke, S.Hausler, J.B.Engel, E.Horn, K.Nurnberger, J.Wischhusen, J.Dietl, A.Honig. Macrophage migration-inhibitory factor levels in serum of patients with ovarian cancer correlates with poor prognosis. Anticancer Res 2012; 32:5233-8; PMID:23225421
63. E.Sato, S.H.Olson, J.Ahn, B.Bundy, H.Nishikawa, F.Qian, A.A.Jungbluth, D.Frosina, S.Gnjatic, C.Ambrosone, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 2005; 102:18538-43; PMID:16344461; http://dx.doi.org/10.1073/pnas.0509182102
64. N.Leffers, M.J.Gooden, R.A.de Jong, B.N.Hoogeboom, K.A.ten Hoor, H.Hollema, H.M.Boezen, A.G.van der Zee, T.Daemen, H.W.Nijman. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother 2009; 58:449-59; PMID:18791714; http://dx.doi.org/10.1007/s00262-008-0583-5
65. K.Milne, M.Kobel, S.E.Kalloger, R.O.Barnes, D.Gao, C.B.Gilks, P.H.Watson, B.H.Nelson. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 2009; 4:e6412; PMID:19641607; http://dx.doi.org/10.1371/journal.pone.0006412
66. J.N.McAlpine, H.Porter, M.Kobel, B.H.Nelson, L.M.Prentice, S.E.Kalloger, J.Senz, K.Milne, J.Ding, S.P.Shah, et al. BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma. Mod Pathol 2012; 25:740-50; PMID:22282309; http://dx.doi.org/10.1038/modpathol.2011.211
67. J.Matsuzaki, S.Gnjatic, P.Mhawech-Fauceglia, A.Beck, A.Miller, T.Tsuji, C.Eppolito, F.Qian, S.Lele, P.Shrikant, et al. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A 2010; 107:7875-80; PMID:20385810; http://dx.doi.org/10.1073/pnas.1003345107
68. J.Hamanishi, M.Mandai, M.Iwasaki, T.Okazaki, Y.Tanaka, K.Yamaguchi, T.Higuchi, H.Yagi, K.Takakura, N.Minato, 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 U S A 2007; 104:3360-5; PMID:17360651; http://dx.doi.org/10.1073/pnas.0611533104
69. R.J.Greenwald, G.J.Freeman, A.H.Sharpe. The B7 family revisited. Annu Rev Immunol 2005; 23:515-48; PMID:15771580; http://dx.doi.org/10.1146/annurev.immunol.23.021704.115611
70. M.J.Gooden, T.van Hall. Infiltrating CTLs are bothered by HLA-E on tumors. Oncoimmunology 2012; 1:92-3; PMID:22720221; http://dx.doi.org/10.4161/onci.1.1.17961
71. M.J.Gooden, M.Lampen, E.S.Jordanova, N.Leffers, J.B.Trimbos, S.H.van der Burg, H.Nijman, T.van Hall. HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8+ T lymphocytes. Proc Natl Acad Sci U S A 2011; 108:10656-61; PMID:21670276; http://dx.doi.org/10.1073/pnas.1100354108
72. A.Wilson, F.Radtke. Multiple functions of Notch signaling in self-renewing organs and cancer. FEBS Lett 2006; 580:2860-8; PMID:16574107; http://dx.doi.org/10.1016/j.febslet.2006.03.024
73. M.Yan, G.D.Plowman. Delta-like 4/Notch signaling and its therapeutic implications. Clin Cancer Res 2007; 13:7243-6; PMID:18094402; http://dx.doi.org/10.1158/1078-0432.CCR-07-1393
74. S.Reinartz, S.Kohler, H.Schlebusch, K.Krista, P.Giffels, K.Renke, J.Huober, V.Mobus, R.Kreienberg, A.DuBois, et al. Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125:immunological response and survival (phase Ib/II). Clin Cancer Res 2004; 10:1580-7; PMID:15014007; http://dx.doi.org/10.1158/1078-0432.CCR-03-0056
75. P.Sabbatini, P.Harter, G.Scambia, J.Sehouli, W.Meier, P.Wimberger, K.H.Baumann, C.Kurzeder, B.Schmalfeldt, D.Cibula, et al. Abagovomab as maintenance therapy in patients with epithelial ovarian cancer:a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO–the MIMOSA study. J Clin Oncol 2013; 31:1554-61; PMID:23478059; http://dx.doi.org/10.1200/JCO.2012.46.4057
76. A.A.Noujaim, B.C.Schultes, R.P.Baum, R.Madiyalakan. Induction of CA125-specific B and T cell responses in patients injected with MAb-B43.13–evidence for antibody-mediated antigen-processing and presentation of CA125 in vivo. Cancer Biother Radiopharm 2001; 16:187-203; PMID:11471484; http://dx.doi.org/10.1089/10849780152389384
77. A.N.Gordon, B.C.Schultes, H.Gallion, R.Edwards, T.L.Whiteside, J.M.Cermak, C.F.Nicodemus. CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients. Gynecol Oncol 2004; 94:340-51; PMID:15297171; http://dx.doi.org/10.1016/j.ygyno.2004.04.024
78. T.G.Ehlen, P.J.Hoskins, D.Miller, T.L.Whiteside, C.F.Nicodemus, B.C.Schultes, K.D.Swenerton. A pilot phase 2 study of oregovomab murine monoclonal antibody to CA125 as an immunotherapeutic agent for recurrent ovarian cancer. Int J Gynecol Cancer 2005; 15:1023-34; PMID:16343178; http://dx.doi.org/10.1111/j.1525-1438.2005.00483.x
79. J.Berek, P.Taylor, W.McGuire, L.M.Smith, B.Schultes, C.F.Nicodemus. Oregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer. J Clin Oncol 2009; 27:418-25; PMID:19075271; http://dx.doi.org/10.1200/JCO.2008.17.8400
80. S.Nicholson, C.C.Bomphray, H.Thomas, A.McIndoe, D.Barton, M.Gore, A.J.George. A phase I trial of idiotypic vaccination with HMFG1 in ovarian cancer. Cancer Immunol Immunother 2004; 53:809-16; PMID:15127236; http://dx.doi.org/10.1007/s00262-004-0522-z
81. R.H.Verheijen, L.F.Massuger, B.B.Benigno, A.A.Epenetos, A.Lopes, J.T.Soper, J.Markowska, R.Vyzula, T.Jobling, G.Stamp, et al. Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine monoclonal antibody in patients with epithelial ovarian cancer after a surgically defined complete remission. J Clin Oncol 2006; 24:571-8; PMID:16446329; http://dx.doi.org/10.1200/JCO.2005.02.5973
82. W.Fiedler, S.DeDosso, S.Cresta, J.Weidmann, A.Tessari, M.Salzberg, B.Dietrich, H.Baumeister, S.Goletz, L.Gianni, et al. A phase I study of PankoMab-GEX, a humanised glyco-optimised monoclonal antibody to a novel tumour-specific MUC1 glycopeptide epitope in patients with advanced carcinomas. Eur J Cancer 2016; 63:55-63; PMID:27285281; http://dx.doi.org/10.1016/j.ejca.2016.05.003
83. A.Burges, P.Wimberger, C.Kumper, V.Gorbounova, H.Sommer, B.Schmalfeldt, J.Pfisterer, M.Lichinitser, A.Makhson, V.Moiseyenko, et al. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody:a phase I/II study. Clin Cancer Res 2007; 13:3899-905; PMID:17606723; http://dx.doi.org/10.1158/1078-0432.CCR-06-2769
84. P.Hoffmann, R.Hofmeister, K.Brischwein, C.Brandl, S.Crommer, R.Bargou, C.Itin, N.Prang, P.A.Baeuerle. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int J Cancer 2005; 115:98-104; PMID:15688411; http://dx.doi.org/10.1002/ijc.20908
85. M.M.Heiss, P.Murawa, P.Koralewski, E.Kutarska, O.O.Kolesnik, V.V.Ivanchenko, A.S.Dudnichenko, B.Aleknaviciene, A.Razbadauskas, M.Gore, et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer:Results of a prospective randomized phase II/III trial. Int J Cancer 2010; 127:2209-21; PMID:20473913; http://dx.doi.org/10.1002/ijc.25423
86. L.R.Coney, D.Mezzanzanica, D.Sanborn, P.Casalini, M.I.Colnaghi, V.R.Zurawski, Jr. Chimeric murine-human antibodies directed against folate binding receptor are efficient mediators of ovarian carcinoma cell killing. Cancer Res 1994; 54:2448-55; PMID:7512887
87. F.Crippa, G.Bolis, E.Seregni, N.Gavoni, G.Scarfone, C.Ferraris, G.L.Buraggi, E.Bombardieri. Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal antibody I-131 MOv18:clinical results in patients with minimal residual disease of ovarian cancer. Eur J Cancer 1995; 31A:686-90; PMID:7640039; http://dx.doi.org/10.1016/0959-8049(94)00454-D
88. M.R.Buist, P.Kenemans, W.den Hollander, J.B.Vermorken, C.J.Molthoff, C.W.Burger, T.J.Helmerhorst, J.P.Baak, J.C.Roos. Kinetics and tissue distribution of the radiolabeled chimeric monoclonal antibody MOv18 IgG and F(ab')2 fragments in ovarian carcinoma patients. Cancer Res 1993; 53:5413-8; PMID:8221680
89. C.F.Molthoff, H.M.Prinssen, P.Kenemans, A.C.van Hof, W.den Hollander, R.H.Verheijen. Escalating protein doses of chimeric monoclonal antibody MOv18 immunoglobulin G in ovarian carcinoma patients:a phase I study. Cancer 1997; 80:2712-20; PMID:9406729; http://dx.doi.org/10.1002/(SICI)1097-0142(19971215)80:12+%3c2712::AID-CNCR50%3e3.3.CO;2-M
90. W.C.Buijs, J.G.Tibben, O.C.Boerman, C.F.Molthoff, L.F.Massuger, E.B.Koenders, C.P.Schijf, J.A.Siegel, F.H.Corstens. Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration. Eur J Nucl Med 1998; 25:1552-61; PMID:9799353; http://dx.doi.org/10.1007/s002590050335
91. I.van Zanten-Przybysz, C.F.Molthoff, J.C.Roos, R.H.Verheijen, A.van Hof, M.R.Buist, H.M.Prinssen, W.den Hollander, P.Kenemans. Influence of the route of administration on targeting of ovarian cancer with the chimeric monoclonal antibody MOv18:i.v. vs. i.p. Int J Cancer 2001; 92:106-14; PMID:11279613
92. Y.Wen, W.S.Graybill, R.A.Previs, W.Hu, C.Ivan, L.S.Mangala, B.Zand, A.M.Nick, N.B.Jennings, H.J.Dalton, et al. Immunotherapy targeting folate receptor induces cell death associated with autophagy in ovarian cancer. Clin Cancer Res 2015; 21:448-59; PMID:25416196; http://dx.doi.org/10.1158/1078-0432.CCR-14-1578
93. B.A.Kamen, A.K.Smith. Farletuzumab, an anti-folate receptor alpha antibody, does not block binding of folate or anti-folates to receptor nor does it alter the potency of anti-folates in vitro. Cancer Chemother Pharmacol 2012; 70:113-20; PMID:22644798; http://dx.doi.org/10.1007/s00280-012-1890-2
94. J.A.Konner, K.M.Bell-McGuinn, P.Sabbatini, M.L.Hensley, W.P.Tew, N.Pandit-Taskar, N.Vander Els, M.D.Phillips, C.Schweizer, S.C.Weil, et al. Farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer:a phase I study. Clin Cancer Res 2010; 16:5288-95; PMID:20855460; http://dx.doi.org/10.1158/1078-0432.CCR-10-0700
95. K.H.Kim, D.Jelovac, D.K.Armstrong, B.Schwartz, S.C.Weil, C.Schweizer, R.D.Alvarez. Phase 1b safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer. Gynecol Oncol 2016; 140:210-4; PMID:26644263; http://dx.doi.org/10.1016/j.ygyno.2015.11.031
96. D.K.Armstrong, A.J.White, S.C.Weil, M.Phillips, R.L.Coleman. Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer. Gynecol Oncol 2013; 129:452-8; PMID:23474348; http://dx.doi.org/10.1016/j.ygyno.2013.03.002
97. Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, et al. A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse. J Clin Oncol 2016; 34:2271–8. PMID:27001568 doi:10.1200/JCO.2015.63.2596
98. C.Marchetti, I.Palaia, M.Giorgini, C.De Medici, R.Iadarola, L.Vertechy, L.Domenici, V.Di Donato, F.Tomao, L.Muzii, et al. Targeted drug delivery via folate receptors in recurrent ovarian cancer:a review. Onco Targets Ther 2014; 7:1223-36; PMID:25031539; http://dx.doi.org/10.2147/OTT.S40947
99. R.Hassan, W.Ebel, E.L.Routhier, R.Patel, J.B.Kline, J.Zhang, Q.Chao, S.Jacob, H.Turchin, L.Gibbs, et al. Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin. Cancer Immun 2007; 7:20; PMID:18088084
100. R.Hassan, S.J.Cohen, M.Phillips, I.Pastan, E.Sharon, R.J.Kelly, C.Schweizer, S.Weil, D.Laheru. Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers. Clin Cancer Res 2010; 16:6132-8; PMID:21037025; http://dx.doi.org/10.1158/1078-0432.CCR-10-2275
101. D.Patel, A.Lahiji, S.Patel, M.Franklin, X.Jimenez, D.J.Hicklin, X.Kang. Monoclonal antibody cetuximab binds to and down-regulates constitutively activated epidermal growth factor receptor vIII on the cell surface. Anticancer Res 2007; 27:3355-66; PMID:17970081
102. J.Mendelsohn, J.Baselga. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 2003; 21:2787-99; PMID:12860957; http://dx.doi.org/10.1200/JCO.2003.01.504
103. R.J.Schilder, H.B.Pathak, A.E.Lokshin, R.W.Holloway, R.D.Alvarez, C.Aghajanian, H.Min, K.Devarajan, E.Ross, C.W.Drescher, et al. Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash. Gynecol Oncol 2009; 113:21-7; PMID:19162309; http://dx.doi.org/10.1016/j.ygyno.2008.12.003
104. J.Konner, R.J.Schilder, F.A.DeRosa, S.R.Gerst, W.P.Tew, P.J.Sabbatini, M.L.Hensley, D.R.Spriggs, C.A.Aghajanian. A phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advanced-stage ovarian, primary peritoneal, or fallopian tube cancer. Gynecol Oncol 2008; 110:140-5; PMID:18554700; http://dx.doi.org/10.1016/j.ygyno.2008.04.018
105. A.A.Secord, J.A.Blessing, D.K.Armstrong, W.H.Rodgers, Z.Miner, M.N.Barnes, G.Lewandowski, R.S.Mannel. Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression:a Gynecologic Oncology Group study. Gynecol Oncol 2008; 108:493-9; PMID:18191993; http://dx.doi.org/10.1016/j.ygyno.2007.11.029
106. M.Wu, A.Rivkin, T.Pham. Panitumumab:human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin Ther 2008; 30:14-30; PMID:18343240; http://dx.doi.org/10.1016/j.clinthera.2008.01.014
107. G.Vlahovic, K.L.Meadows, H.E.Uronis, M.A.Morse, G.C.Blobe, R.F.Riedel, S.Y.Zafar, A.Alvarez-Secord, J.Gockerman, A.N.Starodub, et al. A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors. Cancer Chemother Pharmacol 2012; 70:95-102; PMID:22638798; http://dx.doi.org/10.1007/s00280-012-1889-8
108. K.D.Steffensen, M.Waldstrom, N.Pallisgard, B.Lund, K.Bergfeldt, J.Wihl, N.Keldsen, C.Marth, I.Vergote, A.Jakobsen. Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type:the PaLiDo study, a phase II nonrandomized multicenter study. Int J Gynecol Cancer 2013; 23:73-80; PMID:23211422; http://dx.doi.org/10.1097/IGC.0b013e3182775fae
109. M.V.Seiden, H.A.Burris, U.Matulonis, J.B.Hall, D.K.Armstrong, J.Speyer, J.D.Weber, F.Muggia. A phase II trial of EMD72000 (matuzumab), a humanized anti-EGFR monoclonal antibody, in patients with platinum-resistant ovarian and primary peritoneal malignancies. Gynecol Oncol 2007; 104:727-31; PMID:17126894; http://dx.doi.org/10.1016/j.ygyno.2006.10.019
110. U.Vanhoefer, M.Tewes, F.Rojo, O.Dirsch, N.Schleucher, O.Rosen, J.Tillner, A.Kovar, A.H.Braun, T.Trarbach, et al. Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor. J Clin Oncol 2004; 22:175-84; PMID:14701780; http://dx.doi.org/10.1200/JCO.2004.05.114
111. M.A.Bookman, K.M.Darcy, D.Clarke-Pearson, R.A.Boothby, I.R.Horowitz. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2:a phase II trial of the Gynecologic Oncology Group. J Clin Oncol 2003; 21:283-90; PMID:12525520; http://dx.doi.org/10.1200/JCO.2003.10.104
112. D.Wuerkenbieke, J.Wang, Y.Li, C.Ma. miRNA-150 downregulation promotes pertuzumab resistance in ovarian cancer cells via AKT activation. Arch Gynecol Obstet 2015; 292:1109-16; PMID:25986891; http://dx.doi.org/10.1007/s00404-015-3742-x
113. P.Mullen, D.A.Cameron, M.Hasmann, J.F.Smyth, S.P.Langdon. Sensitivity to pertuzumab (2C4) in ovarian cancer models:cross-talk with estrogen receptor signaling. Mol Cancer Ther 2007; 6:93-100; PMID:17237269; http://dx.doi.org/10.1158/1535-7163.MCT-06-0401
114. N.Takai, A.Jain, N.Kawamata, L.M.Popoviciu, J.W.Said, S.Whittaker, I.Miyakawa, D.B.Agus, H.P.Koeffler. 2C4, a monoclonal antibody against HER2, disrupts the HER kinase signaling pathway and inhibits ovarian carcinoma cell growth. Cancer 2005; 104:2701-8; PMID:16265675; http://dx.doi.org/10.1002/cncr.21533
115. S.Makhija, L.C.Amler, D.Glenn, F.R.Ueland, M.A.Gold, D.S.Dizon, V.Paton, C.Y.Lin, T.Januario, K.Ng, et al. Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. J Clin Oncol 2010; 28:1215-23; PMID:19901115; http://dx.doi.org/10.1200/JCO.2009.22.3354
116. Y.Nagumo, D.Faratian, P.Mullen, D.J.Harrison, M.Hasmann, S.P.Langdon. Modulation of HER3 is a marker of dynamic cell signaling in ovarian cancer:implications for pertuzumab sensitivity. Mol Cancer Res 2009; 7:1563-71; PMID:19737968; http://dx.doi.org/10.1158/1541-7786.MCR-09-0101
117. D.B.Agus, M.S.Gordon, C.Taylor, R.B.Natale, B.Karlan, D.S.Mendelson, M.F.Press, D.E.Allison, M.X.Sliwkowski, G.Lieberman, et al. Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol 2005; 23:2534-43; PMID:15699478; http://dx.doi.org/10.1200/JCO.2005.03.184
118. M.S.Gordon, D.Matei, C.Aghajanian, U.A.Matulonis, M.Brewer, G.F.Fleming, J.D.Hainsworth, A.A.Garcia, M.D.Pegram, R.J.Schilder, et al. Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer:potential predictive relationship with tumor HER2 activation status. J Clin Oncol 2006; 24:4324-32; PMID:16896006; http://dx.doi.org/10.1200/JCO.2005.05.4221
119. S.B.Kaye, C.J.Poole, M.Bidzinski, L.Gianni, V.Gorbunova, E.Novikova, A.Strauss, V.A.McNally, G.Ross, I.Vergote. A randomised phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab (P) versus carboplatin-based therapy alone in patients with relapsed, platinum-sensitive ovarian cancer. J Clin Oncol 2008; 26:15s 5520; http://dx.doi.org/10.1200/JCO.2008.16.2123
120. J.Huang, S.Wang, H.Lyu, B.Cai, X.Yang, J.Wang, B.Liu. The anti-erbB3 antibody MM-121/SAR256212 in combination with trastuzumab exerts potent antitumor activity against trastuzumab-resistant breast cancer cells. Mol Cancer 2013; 12:134; PMID:24215614; http://dx.doi.org/10.1186/1476-4598-12-134
121. J.Liu, I.L.Ray-Coquard, F.Selle, A.Poveda, D.Cibula, H.W.Hirte, F.Raspagliesi, L.Gladieff, P.Harter, I.Schiavetto, et al. A phase II randomized open-label study of MM-121, a fully human monoclonal antibody targeting ErbB3, in combination with weekly paclitaxel versus weekly paclitaxel in patients with platinum-resistant/refractory ovarian cancers. J Clin Oncol 2014; 32:5s 5519; http://dx.doi.org/10.1200/JCO.2013.49.4757
122. E.G.Chiorean, C.Sweeney, H.Youssoufian, A.Qin, A.Dontabhaktuni, N.Loizos, J.Nippgen, R.Amato. A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRalpha) monoclonal antibody, in patients with advanced solid tumors. Cancer Chemother Pharmacol 2014; 73:595-604; PMID:24452395; http://dx.doi.org/10.1007/s00280-014-2389-9
123. K.Matsuo, M.Nishimura, K.Komurov, M.M.K.Shahzad, R.Ali-Fehmi, J.W.Roh, C.H.Lu, D.D.Cody, P.T.Ram, N.Loizos, et al. Platelet-derived growth factor receptor alpha (PDGFR alpha) targeting and relevant biomarkers in ovarian carcinoma. Gynecol Oncol 2014; 132:166-75; PMID:24183729; http://dx.doi.org/10.1016/j.ygyno.2013.10.027
124. A.T.Byrne, L.Ross, J.Holash, M.Nakanishi, L.Hu, J.I.Hofmann, G.D.Yancopoulos, R.B.Jaffe. Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res 2003; 9:5721-8; PMID:14654557
125. R.A.Burger, M.W.Sill, B.J.Monk, B.E.Greer, J.I.Sorosky. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer:a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25:5165-71; PMID:18024863; http://dx.doi.org/10.1200/JCO.2007.11.5345
126. R.A.Burger. Role of vascular endothelial growth factor inhibitors in the treatment of gynecologic malignancies. J Clin Oncol 2010; 21:3-11; PMID:20379441; http://dx.doi.org/10.3802/jgo.2010.21.1.3
127. T.J.Perren, A.M.Swart, J.Pfisterer, J.A.Ledermann, E.Pujade-Lauraine, G.Kristensen, M.S.Carey, P.Beale, A.Cervantes, C.Kurzeder, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011; 365:2484-96; PMID:22204725; http://dx.doi.org/10.1056/NEJMoa1103799
128. E.Pujade-Lauraine, F.Hilpert, B.Weber, A.Reuss, A.Poveda, G.Kristensen, R.Sorio, I.Vergote, P.Witteveen, A.Bamias, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer:The AURELIA open-label randomized phase III trial. J Clin Oncol 2014; 32:1302-8; PMID:24637997; http://dx.doi.org/10.1200/JCO.2013.51.4489
129. K.Sawada, A.K.Mitra, A.R.Radjabi, V.Bhaskar, E.O.Kistner, M.Tretiakova, S.Jagadeeswaran, A.Montag, A.Becker, H.A.Kenny, et al. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res 2008; 68:2329-39; PMID:18381440; http://dx.doi.org/10.1158/0008-5472.CAN-07-5167
130. A.D.Ricart, A.W.Tolcher, G.Liu, K.Holen, G.Schwartz, M.Albertini, G.Weiss, S.Yazji, C.Ng, G.Wilding. Volociximab, a chimeric monoclonal antibody that specifically binds alpha5beta1 integrin:a phase I, pharmacokinetic, and biological correlative study. Clin Cancer Res 2008; 14:7924-9; PMID:19047123; http://dx.doi.org/10.1158/1078-0432.CCR-08-0378
131. K.M.Bell-McGuinn, C.M.Matthews, S.N.Ho, M.Barve, L.Gilbert, R.T.Penson, E.Lengyel, R.Palaparthy, K.Gilder, A.Vassos, et al. A phase II, single-arm study of the anti-alpha5beta1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer. Gynecol Oncol 2011; 121:273-9; PMID:21276608; http://dx.doi.org/10.1016/j.ygyno.2010.12.362
132. I.Vergote, N.Colombo, E.Kutarska, J.del Campo, C.Pippitt, A.Casado, E.Lengyel, K.Gilder, S.Ho, R.J.Schilder. Phase II study comparing volociximab (an antiangiogenic antibody) and pegylated liposomal doxorubicin (PLD) with PLD alone in recurrent ovarian or primary peritoneal cancer. J Clin Oncol 2009; 27:15s 5560; http://dx.doi.org/10.1200/JCO.2009.23.9822
133. A.N.Gordon, J.T.Fleagle, D.Guthrie, D.E.Parkin, M.E.Gore, A.J.Lacave. Recurrent epithelial ovarian carcinoma:a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 2001; 19:3312-22; PMID:11454878
134. E.Angevin, J.Tabernero, E.Elez, S.J.Cohen, R.Bahleda, J.L.van Laethem, C.Ottensmeier, J.A.Lopez-Martin, S.Clive, F.Joly, et al. A phase I/II, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res 2014; 20:2192-204; PMID:24563479; http://dx.doi.org/10.1158/1078-0432.CCR-13-2200
135. D.Mahalingam, R.M.Patel, J.C.Sachdev, L.L.Hart, N.Halama, R.K.Ramanathan, J.Sarantopoulos, X.Liu, S.Yazji, D.Jaeger, et al. First-in-human, phase I study assessing imalumab (Bax69), a first-in-class anti-oxidized macrophage migration inhibitory factor (oxMIF) antibody in advanced solid tumors. J Clin Oncol 2015; 33:2518.
136. S.L.Topalian, F.S.Hodi, J.R.Brahmer, S.N.Gettinger, D.C.Smith, D.F.McDermott, J.D.Powderly, R.D.Carvajal, J.A.Sosman, M.B.Atkins, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366:2443-54; PMID:22658127; http://dx.doi.org/10.1056/NEJMoa1200690
137. J.Hamanishi, M.Mandai, T.Ikeda, M.Minami, A.Kawaguchi, T.Murayama, M.Kanai, Y.Mori, S.Matsumoto, S.Chikuma, et al. Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. J Clin Oncol 2015; 33:4015-22; PMID:26351349; http://dx.doi.org/10.1200/JCO.2015.62.3397
138. A.Varga, S.A.Piha-Paul, P.A.Ott. Antitumour activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer:interim results from a phase Ib study. J Clin Oncol 2015; 33:5510.
139. J.R.Brahmer, S.S.Tykodi, L.Q.Chow, W.J.Hwu, S.L.Topalian, P.Hwu, C.G.Drake, L.H.Camacho, J.Kauh, K.Odunsi, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366:2455-65; PMID:22658128; http://dx.doi.org/10.1056/NEJMoa1200694
140. M.L.Disis, M.R.Patel, S.Pant, J.R.Infante, A.C.Lockhart, K.Kelly, J.T.Beck, M.S.Gordon, G.J.Weiss, S.Ejadi, et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer:A phase Ib, open-label expansion trial. J Clin Oncol 2015; 33:15s 5509.
141. F.S.Hodi, M.C.Mihm, R.J.Soiffer, F.G.Haluska, M.Butler, M.V.Seiden, T.Davis, R.Henry-Spires, S.MacRae, A.Willman, 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 U S A 2003; 100:4712-7; PMID:12682289; http://dx.doi.org/10.1073/pnas.0830997100
142. F.S.Hodi, M.Butler, D.A.Oble, M.V.Seiden, F.G.Haluska, A.Kruse, S.Macrae, M.Nelson, C.Canning, I.Lowy, et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A 2008; 105:3005-10; PMID:18287062; http://dx.doi.org/10.1073/pnas.0712237105
143. M.K.Callahan, P.A.Ott, K.Odunsi, S.V.Bertolini, L.S.Pan, R.R.Venhaus, J.J.Karakunnel, F.S.Hodi, J.D.Wolchok. A phase 1 study to evaluate the safety and tolerability of MEDI4736, an anti–PD-L1 antibody, in combination with tremelimumab in patients with advanced solid tumors. J Clin Oncol 2014; 32:5s TPS3120; http://dx.doi.org/10.1200/JCO.2013.49.4757
144. L.Seymour, A.Tinker, H.Hirte, N.Wagtmann, P.Dodion. Phase I and dose ranging, phase II studies with IPH2201, a humanized monoclonal antibody targeting HLA-E receptor CD94/NKG2A. Ann Oncol 2015; 26 (suppl 2):ii3; http://dx.doi.org/10.1093/annonc/mdv081.2
145. D.C.Smith, P.D.Eisenberg, G.Manikhas, R.Chugh, M.A.Gubens, R.J.Stagg, A.M.Kapoun, L.Xu, J.Dupont, B.Sikic. A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Clin Cancer Res 2014; 20:6295-303; PMID:25324140; http://dx.doi.org/10.1158/1078-0432.CCR-14-1373
146. A.Mullard. Maturing antibody-drug conjugate pipeline hits 30. Nat Rev Drug Discov 2013; 12:329-32; PMID:23629491; http://dx.doi.org/10.1038/nrd4009
147. O.Ab, K.R.Whiteman, L.M.Bartle, X.Sun, R.Singh, D.Tavares, A.LaBelle, G.Payne, R.J.Lutz, J.Pinkas, et al. IMGN853, a Folate Receptor-alpha (FRalpha)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRalpha-Expressing Tumors. Mol Cancer Ther 2015; 14:1605-13; PMID:25904506; http://dx.doi.org/10.1158/1535-7163.MCT-14-1095
148. H.Borghael, D.O'Malley, S.M.Seward, T.M.Bauer, R.P.Perez, A.M.Oza, W.Jeong, M.F.Michenzie, M.W.Kirby, G.Chandorkar, et al. Phase 1 study of IMGN853, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) in patients (Pts) with epithelial ovarian cancer (EOC) and other FRA-positive solid tumors. J Clin Oncol 2015; 33:15s 5558.
149. S.Lindegren, L.N.Andrade, T.Back, C.M.Machado, B.B.Horta, C.Buchpiguel, A.M.Moro, O.K.Okamoto, L.Jacobsson, E.Cederkrantz, et al. Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200. PLoS One 2015; 10:e0126298; PMID:25970341; http://dx.doi.org/10.1371/journal.pone.0126298
150. H.A.Burris, M.S.Gordon, D.E.Gerber, D.R.Spigel, D.S.Mendelson, J.H.Schiller, Y.Wang, Y.Choi, R.S.Kahn, K.Wood, et al. A phase I study of DNIB0600A, an antibody-drug conjugate (ADC) targeting NaPi2b, in patients (pts) with non-small cell lung cancer (NSCLC) or platinum-resistant ovarian cancer (OC). J Clin Oncol 2014; 32:5s 2504; http://dx.doi.org/10.1200/JCO.2013.49.4757
151. D.S.Hong, I.Garrido-Laguna, I.E.Krop, V.Subbiah, T.W.Werner, C.M.Cotter, E.P.Hamilton, K.Velastegul, D.Xuan, R.Bugarini, et al. First-in-human dose escalation, safety, and PK study of a novel EFNA4-ADC in patients with advanced solid tumors. J Clin Oncol 2015; 33:15s 2520; http://dx.doi.org/10.1200/JCO.2015.60.8554
152. NCI. NCI Thesaurus. https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C124133. 2016.
153. U.Sahin, D.Jaeger, F.Marme, A.Mavratzas, J.Krauss, J.De Greve, I.Vergote, O.Tureci. First-in-human phase I/II dose-escalation study of IMAB027 in patients with recurrent advanced ovarian cancer (OVAR):Preliminary data of phase I part. J Clin Oncol 2015; 33:5537.
154. H.J.Gould, G.A.Mackay, S.N.Karagiannis, C.M.O'Toole, P.J.Marsh, B.E.Daniel, L.R.Coney, V.R.Zurawski, Jr., M.Joseph, M.Capron, et al. Comparison of IgE and IgG antibody-dependent cytotoxicity in vitro and in a SCID mouse xenograft model of ovarian carcinoma. Eur J Immunol 1999; 29:3527-37; PMID:10556807; http://dx.doi.org/10.1002/(SICI)1521-4141(199911)29:11%3c3527::AID-IMMU3527%3e3.0.CO;2-5
155. D.H.Josephs, J.F.Spicer, P.Karagiannis, H.J.Gould, S.N.Karagiannis. IgE immunotherapy:a novel concept with promise for the treatment of cancer. MAbs 2014; 6:54-72; PMID:24423620; http://dx.doi.org/10.4161/mabs.27029
156. S.N.Karagiannis, Q.Wang, N.East, F.Burke, S.Riffard, M.G.Bracher, R.G.Thompson, S.R.Durham, L.B.Schwartz, F.R.Balkwill, et al. Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells. Eur J Immunol 2003; 33:1030-40; PMID:12672069; http://dx.doi.org/10.1002/eji.200323185
157. S.N.Karagiannis, M.G.Bracher, J.Hunt, N.McCloskey, R.L.Beavil, A.J.Beavil, D.J.Fear, R.G.Thompson, N.East, F.Burke, et al. IgE-antibody-dependent immunotherapy of solid tumors:cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells. J Immunol 2007; 179:2832-43; PMID:17709497; http://dx.doi.org/10.4049/jimmunol.179.5.2832
158. R.Jefferis. Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov 2009; 8:226-34; PMID:19247305; http://dx.doi.org/10.1038/nrd2804
159. A.M.Scott, J.D.Wolchok, L.J.Old. Antibody therapy of cancer. Nat Rev Cancer 2012; 12:278-87; PMID:22437872; http://dx.doi.org/10.1038/nrc3236
160. M.Bruggemann, G.T.Williams, C.I.Bindon, M.R.Clark, M.R.Walker, R.Jefferis, H.Waldmann, M.S.Neuberger. Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med 1987; 166:1351-61; PMID:3500259; http://dx.doi.org/10.1084/jem.166.5.1351
161. G.P.Dunn, A.T.Bruce, H.Ikeda, L.J.Old, R.D.Schreiber. Cancer immunoediting:from immunosurveillance to tumor escape. Nat Immunol 2002; 3:991-8; PMID:12407406; http://dx.doi.org/10.1038/ni1102-991
162. J.Duraiswamy, K.M.Kaluza, G.J.Freeman, G.Coukos. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res 2013; 73:3591-603; PMID:23633484; http://dx.doi.org/10.1158/0008-5472.CAN-12-4100
163. L.E.Kandalaft, D.J.Powell, Jr., C.L.Chiang, J.Tanyi, S.Kim, M.Bosch, K.Montone, R.Mick, B.L.Levine, D.A.Torigian, et al. Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer. Oncoimmunology 2013; 2:e22664; PMID:23482679; http://dx.doi.org/10.4161/onci.22664