Recent advances of bispecific antibodies in solid tumors

Journal of Hematology and Oncology

Volumn 10, Issue 1, 2017, Pages

  Han, Xinwei ^b   Yu, Shengnan ^a   Li, Anping ^b   Liu, Qian ^a   Yuan, Xun ^a   Xu, Hanxiao ^a   Jiao, Dechao ^b   Pestell, Richard G ^c   Wu, Kongming ^a  

^a HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIVERSITY   (China)

^c Pennsylvania Cancer and Regenerative Medicine Research Center   (United States)

Author keywords

BsAb; CEA; EpCAM; HER family; PSMA; Radioimmunotherapy; Solid tumor

Indexed keywords

BISPECIFIC ANTIBODY; CARCINOEMBRYONIC ANTIGEN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPITHELIAL CELL ADHESION MOLECULE; PROSTATE SPECIFIC MEMBRANE ANTIGEN;

ANTIGEN EXPRESSION; CANCER IMMUNOTHERAPY; DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; HUMAN; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); REVIEW; SOLID MALIGNANT NEOPLASM; GENETICS; IMMUNOTHERAPY; METABOLISM; NEOPLASM; PROCEDURES;

ANTIBODIES, BISPECIFIC; HUMANS; IMMUNOTHERAPY; NEOPLASMS;

EID: 85029690874     PISSN: None     EISSN: 17568722     Source Type: Journal    
DOI: 10.1186/s13045-017-0522-z     Document Type: Review

References (155)

1. Jia Y, Yun CH, Park E, Ercan D, Manuia M, Juarez J, et al. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016;534(7605):129-32.
2. Goel G, Sun W. Novel approaches in the management of pancreatic ductal adenocarcinoma: potential promises for the future. J Hematol Oncol. 2015;8:44.
3. Ma W, Gilligan BM, Yuan J, Li T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol. 2016;9(1):47.
4. Goel G, Sun W. Advances in the management of gastrointestinal cancers - an upcoming role of immune checkpoint blockade. J Hematol Oncol. 2015;8:86.
5. Falchi L, Sawas A, Deng C, Amengual JE, Colbourn DS, Lichtenstein EA, et al. High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy. J Hematol Oncol. 2016;9(1):132.
6. Hirsch FR, Suda K, Wiens J, Bunn PA Jr. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016;388(10048):1012-24.
7. Yu S, Li A, Liu Q, Li T, Yuan X, Han X, et al. Chimeric antigen receptor T cells: a novel therapy for solid tumors. J Hematol Oncol. 2017;10(1):78.
8. Pardoll DM. Immunology beats cancer: a blueprint for successful translation. Nat Immunol. 2012;13(12):1129-32.
9. Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836-47.
10. Spiess C, Zhai Q, Carter PJ. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol Immunol. 2015;67(2 Pt A):95-106.
11. Fan D, Li W, Yang Y, Zhang X, Zhang Q, Yan Y, et al. Redirection of CD4+ and CD8+ T lymphocytes via an anti-CD3× anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells. J Hematol Oncol. 2015;8:108.
12. Wang S, Chen C, Meng Y, Hu S, Zheng L, Song J, et al. Effective suppression of breast tumor growth by an anti-EGFR/ErbB2 bispecific antibody. Cancer Lett. 2012;325(2):214-9.
13. Grugan KD, Dorn K, Jarantow SW, Bushey BS, Pardinas JR, Laquerre S, et al. Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells. MAbs. 2017;9(1):114-26.
14. Fan G, Wang Z, Hao M, Li J. Bispecific antibodies and their applications. J Hematol Oncol. 2015;8:130.
15. Nunez-Prado N, Compte M, Harwood S, Alvarez-Mendez A, Lykkemark S, Sanz L, et al. The coming of age of engineered multivalent antibodies. Drug Discov Today. 2015;20(5):588-94.
16. Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013;17(3):385-92.
17. Suryadevara CM, Gedeon PC, Sanchez-Perez L, Verla T, Alvarez-Breckenridge C, Choi BD, et al. Are BiTEs the "missing link" in cancer therapy? Oncoimmunology. 2015;4(6):e1008339.
18. Wu J, Fu J, Zhang M, Liu D. Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia. J Hematol Oncol. 2015;8:104.
19. Klinger M, Benjamin J, Kischel R, Stienen S, Zugmaier G. Harnessing T cells to fight cancer with BiTE(R) antibody constructs - past developments and future directions. Immunol Rev. 2016;270(1):193-208.
20. May C, Sapra P, Gerber HP. Advances in bispecific biotherapeutics for the treatment of cancer. Biochem Pharmacol. 2012;84(9):1105-12.
21. Morecki S, Lindhofer H, Yacovlev E, Gelfand Y, Slavin S. Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes. Blood. 2006;107(4):1564-9.
22. Goere D, Flament C, Rusakiewicz S, Poirier-Colame V, Kepp O, Martins I, et al. Potent immunomodulatory effects of the trifunctional antibody catumaxomab. Cancer Res. 2013;73(15):4663-73.
23. Haas C, Krinner E, Brischwein K, Hoffmann P, Lutterbuse R, Schlereth B, et al. Mode of cytotoxic action of T cell-engaging BiTE antibody MT110. Immunobiology. 2009;214(6):441-53.
24. Hoffmann P, Hofmeister R, Brischwein K, Brandl C, Crommer S, Bargou R, et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int J Cancer. 2005;115(1):98-104.
25. Ruf P, Gires O, Jager M, Fellinger K, Atz J, Lindhofer H. Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer. Br J Cancer. 2007;97(3):315-21.
26. Wu J, Fu J, Zhang M, Liu D. AFM13: a first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy. J Hematol Oncol. 2015;8:96.
27. Zugmaier G, Klinger M, Schmidt M, Subklewe M. Clinical overview of anti-CD19 BiTE((R)) and ex vivo data from anti-CD33 BiTE((R)) as examples for retargeting T cells in hematologic malignancies. Mol Immunol. 2015;67(2 Pt A):58-66.
28. Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO. Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol. 1994;125(2):437-46.
29. Balzar M, Briaire-de Bruijn IH, Rees-Bakker HA, Prins FA, Helfrich W, de Leij L, et al. Epidermal growth factor-like repeats mediate lateral and reciprocal interactions of Ep-CAM molecules in homophilic adhesions. Mol Cell Biol. 2001;21(7):2570-80.
30. Gonzalez B, Denzel S, Mack B, Conrad M, Gires O. EpCAM is involved in maintenance of the murine embryonic stem cell phenotype. Stem Cells. 2009;27(8):1782-91.
31. Amann M, Brischwein K, Lutterbuese P, Parr L, Petersen L, Lorenczewski G, et al. Therapeutic window of MuS110, a single-chain antibody construct bispecific for murine EpCAM and murine CD3. Cancer Res. 2008;68(1):143-51.
32. Munz M, Baeuerle PA, Gires O. The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res. 2009;69(14):5627-9.
33. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8(10):755-68.
34. Gires O, Klein CA, Baeuerle PA. On the abundance of EpCAM on cancer stem cells. Nat Rev Cancer. 2009;9(2):143. author reply 143
35. Balzar M, Winter MJ, de Boer CJ, Litvinov SV. The biology of the 17-1A antigen (Ep-CAM). J Mol Med. 1999;77(10):699-712.
36. Baeuerle PA, Gires O. EpCAM (CD326) finding its role in cancer. Br J Cancer. 2007;96(3):417-23.
37. Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 2004;23(34):5748-58.
38. Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, et al. Nuclear signaling by tumour-associated antigen EpCAM. Nat Cell Biol. 2009;11(2):162-71.
39. Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, et al. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer. 2006;94(1):128-35.
40. Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, et al. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35(1):122-8.
41. Gastl G, Spizzo G, Obrist P, Dunser M, Mikuz G. Ep-CAM overexpression in breast cancer as a predictor of survival. Lancet. 2000;356(9246):1981-2.
42. Spizzo G, Went P, Dirnhofer S, Obrist P, Simon R, Spichtin H, et al. High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer. Breast Cancer Res Treat. 2004;86(3):207-13.
43. Spizzo G, Went P, Dirnhofer S, Obrist P, Moch H, Baeuerle PA, et al. 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(2):483-8.
44. Schmitt M, Schmitt A, Reinhardt P, Thess B, Manfras B, Lindhofer H, et al. Opsonization with a trifunctional bispecific (alphaCD3 x alphaEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes. Int J Oncol. 2004;25(4):841-8.
45. Seimetz D, Lindhofer H, Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010;36(6):458-67.
46. Hirschhaeuser F, Walenta S, Mueller-Klieser W. Efficacy of catumaxomab in tumor spheroid killing is mediated by its trifunctional mode of action. Cancer Immunol Immunother. 2010;59(11):1675-84.
47. Fossati M, Buzzonetti A, Monego G, Catzola V, Scambia G, Fattorossi A, et al. Immunological changes in the ascites of cancer patients after intraperitoneal administration of the bispecific antibody catumaxomab (anti-EpCAMxanti-CD3). Gynecol Oncol. 2015;138(2):343-51.
48. Mau-Sorensen M, Dittrich C, Dienstmann R, Lassen U, Buchler W, Martinius H, et al. A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3. Cancer Chemother Pharmacol. 2015;75(5):1065-73.
49. Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, 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(9):2209-21.
50. Sebastian M, Passlick B, Friccius-Quecke H, Jager M, Lindhofer H, Kanniess F, et al. Treatment of non-small cell lung cancer patients with the trifunctional monoclonal antibody catumaxomab (anti-EpCAM x anti-CD3): a phase I study. Cancer Immunol Immunother. 2007;56(10):1637-44.
51. Burges A, Wimberger P, Kumper C, Gorbounova V, Sommer H, Schmalfeldt B, 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(13):3899-905.
52. Salnikov AV, Groth A, Apel A, Kallifatidis G, Beckermann BM, Khamidjanov A, et al. Targeting of cancer stem cell marker EpCAM by bispecific antibody EpCAMxCD3 inhibits pancreatic carcinoma. J Cell Mol Med. 2009;13(9b):4023-33.
53. Ferrari F, Bellone S, Black J, Schwab CL, Lopez S, Cocco E, et al. Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE(R)), is highly active against primary uterine and ovarian carcinosarcoma cell lines in vitro. J Exp Clin Cancer Res. 2015;34:123.
54. Martin-Padura I, Marighetti P, Agliano A, Colombo F, Larzabal L, Redrado M, et al. Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts. Lab Investig. 2012;92(7):952-66.
55. Xu XL, Xing BC, Han HB, Zhao W, Hu MH, Xu ZL, et al. The properties of tumor-initiating cells from a hepatocellular carcinoma patient's primary and recurrent tumor. Carcinogenesis. 2010;31(2):167-74.
56. Yamashita T, Budhu A, Forgues M, Wang XW. Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res. 2007;67(22):10831-9.
57. Zhang P, Shi B, Gao H, Jiang H, Kong J, Yan J, et al. An EpCAM/CD3 bispecific antibody efficiently eliminates hepatocellular carcinoma cells with limited galectin-1 expression. Cancer Immunol Immunother. 2014;63(2):121-32.
58. Schlereth B, Fichtner I, Lorenczewski G, Kleindienst P, Brischwein K, da Silva A, et al. Eradication of tumors from a human colon cancer cell line and from ovarian cancer metastases in immunodeficient mice by a single-chain Ep-CAM-/CD3-bispecific antibody construct. Cancer Res. 2005;65(7):2882-9.
59. Herrmann I, Baeuerle PA, Friedrich M, Murr A, Filusch S, Ruttinger D, et al. Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells. PLoS One. 2010;5(10):e13474.
60. Cioffi M, Dorado J, Baeuerle PA, Heeschen C. EpCAM/CD3-Bispecific T-cell engaging antibody MT110 eliminates primary human pancreatic cancer stem cells. Clin Cancer Res. 2012;18(2):465-74.
61. Cioffi M, Heeschen C. Immuno-targeting of pancreatic cancer stem cells: a new therapeutic strategy against a devastating disease? Oncoimmunology. 2012;1(4):560-2.
62. Amann M, Friedrich M, Lutterbuese P, Vieser E, Lorenczewski G, Petersen L, et al. Therapeutic window of an EpCAM/CD3-specific BiTE antibody in mice is determined by a subpopulation of EpCAM-expressing lymphocytes that is absent in humans. Cancer Immunol Immunother. 2009;58(1):95-109.
63. Amann M, D'Argouges S, Lorenczewski G, Brischwein K, Kischel R, Lutterbuese R, et al. Antitumor activity of an EpCAM/CD3-bispecific BiTE antibody during long-term treatment of mice in the absence of T-cell anergy and sustained cytokine release. J Immunother. 2009;32(5):452-64.
64. Vallera DA, Zhang B, Gleason MK, Oh S, Weiner LM, Kaufman DS, et al. Heterodimeric bispecific single-chain variable-fragment antibodies against EpCAM and CD16 induce effective antibody-dependent cellular cytotoxicity against human carcinoma cells. Cancer Biother Radiopharm. 2013;28(4):274-82.
65. Morecki S, Lindhofer H, Yacovlev E, Gelfand Y, Ruf P, Slavin S. Induction of long-lasting antitumor immunity by concomitant cell therapy with allogeneic lymphocytes and trifunctional bispecific antibody. Exp Hematol. 2008;36(8):997-1003.
66. Groth A, Salnikov AV, Ottinger S, Gladkich J, Liu L, Kallifatidis G, et al. New gene-immunotherapy combining TRAIL-lymphocytes and EpCAMxCD3 bispecific antibody for tumor targeting. Clin Cancer Res. 2012;18(4):1028-38.
67. Ren-Heidenreich L, Davol PA, Kouttab NM, Elfenbein GJ, Lum LG. Redirected T-cell cytotoxicity to epithelial cell adhesion molecule-overexpressing adenocarcinomas by a novel recombinant antibody, E3Bi, in vitro and in an animal model. Cancer. 2004;100(5):1095-103.
68. Hoffmann SC, Wabnitz GH, Samstag Y, Moldenhauer G, Ludwig T. Functional analysis of bispecific antibody (EpCAMxCD3)-mediated T-lymphocyte and cancer cell interaction by single-cell force spectroscopy. Int J Cancer. 2011;128(9):2096-104.
69. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127-37.
70. Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9(7):463-75.
71. Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res. 2001;7(10):2958-70.
72. Schoeberl B, Pace EA, Fitzgerald JB, Harms BD, Xu L, Nie L, et al. Therapeutically targeting ErbB3: a key node in ligand-induced activation of the ErbB receptor-PI3K axis. Sci Signal. 2009;2(77):ra31.
73. Wang J, Yin J, Yang Q, Ding F, Chen X, Li B, et al. Human epidermal growth factor receptor 4 (HER4) is a favorable prognostic marker of breast cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(47):76693-703.
74. Rivera F, Vega-Villegas ME, Lopez-Brea MF. Cetuximab, its clinical use and future perspectives. Anti-Cancer Drugs. 2008;19(2):99-113.
75. Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359(17):1757-65.
76. Lutterbuese R, Raum T, Kischel R, Hoffmann P, Mangold S, Rattel B, et al. T cell-engaging BiTE antibodies specific for EGFR potently eliminate KRAS- and BRAF-mutated colorectal cancer cells. Proc Natl Acad Sci U S A. 2010;107(28):12605-10.
77. Berezowska S, Schlegel J. Targeting ErbB receptors in high-grade glioma. Curr Pharm Des. 2011;17(23):2468-87.
78. Zitron IM, Thakur A, Norkina O, Barger GR, Lum LG, Mittal S. Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies. BMC Cancer. 2013;13:83.
79. Ma P, He Q, Li W, Li X, Han H, Jin M, et al. Anti-CD3 x EGFR bispecific antibody redirects cytokine-induced killer cells to glioblastoma in vitro and in vivo. Oncol Rep. 2015;34(5):2567-75.
80. Solomon BJ, Desai J, Rosenthal M, McArthur GA, Pattison ST, Pattison SL, et al. A first-time-in-human phase I clinical trial of bispecific antibody-targeted, paclitaxel-packaged bacterial minicells. PLoS One. 2015;10(12):e0144559.
81. Zhou Y, Gou LT, Guo ZH, Liu HR, Wang JM, Zhou SX, et al. Fully human HER2/cluster of differentiation 3 bispecific antibody triggers potent and specific cytotoxicity of T lymphocytes against breast cancer. Mol Med Rep. 2015;12(1):147-54.
82. Vaishampayan U, Thakur A, Rathore R, Kouttab N, Lum LG. Phase I study of anti-CD3 x anti-Her2 bispecific antibody in metastatic castrate resistant prostate cancer patients. Prostate Cancer. 2015;2015:285193.
83. Lum LG, Thakur A, Al-Kadhimi Z, Colvin GA, Cummings FJ, Legare RD, et al. Targeted T-cell therapy in stage IV breast cancer: a phase I clinical trial. Clin Cancer Res. 2015;21(10):2305-14.
84. Jager M, Schoberth A, Ruf P, Hess J, Lindhofer H. The trifunctional antibody ertumaxomab destroys tumor cells that express low levels of human epidermal growth factor receptor 2. Cancer Res. 2009;69(10):4270-6.
85. Kiewe P, Hasmuller S, Kahlert S, Heinrigs M, Rack B, Marme A, et al. Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin Cancer Res. 2006;12(10):3085-91.
86. Haense N, Atmaca A, Pauligk C, Steinmetz K, Marme F, Haag GM, et al. A phase I trial of the trifunctional anti Her2 x anti CD3 antibody ertumaxomab in patients with advanced solid tumors. BMC Cancer. 2016;16:420.
87. Osaki T, Fujisawa S, Kitaguchi M, Kitamura M, Nakanishi T. Development of a bispecific antibody tetramerized through hetero-associating peptides. FEBS J. 2015;282(22):4389-401.
88. Curnow RT. Clinical experience with CD64-directed immunotherapy. An Overview. Cancer Immunol Immunother. 1997;45(3-4):210-5.
89. Stockmeyer B, Valerius T, Repp R, Heijnen IA, Buhring HJ, Deo YM, et al. Preclinical studies with Fc(gamma)R bispecific antibodies and granulocyte colony-stimulating factor-primed neutrophils as effector cells against HER-2/neu overexpressing breast cancer. Cancer Res. 1997;57(4):696-701.
90. Fury MG, Lipton A, Smith KM, Winston CB, Pfister DG. A phase-I trial of the epidermal growth factor receptor directed bispecific antibody MDX-447 without and with recombinant human granulocyte-colony stimulating factor in patients with advanced solid tumors. Cancer Immunol Immunother. 2008;57(2):155-63.
91. Poovassery JS, Kang JC, Kim D, Ober RJ, Ward ES. Antibody targeting of HER2/HER3 signaling overcomes heregulin-induced resistance to PI3K inhibition in prostate cancer. Int J Cancer. 2015;137(2):267-77.
92. McDonagh CF, Huhalov A, Harms BD, Adams S, Paragas V, Oyama S, et al. Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Mol Cancer Ther. 2012;11(3):582-93.
93. Engelman JA, Janne PA, Mermel C, Pearlberg J, Mukohara T, Fleet C, et al. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines. Proc Natl Acad Sci U S A. 2005;102(10):3788-93.
94. Grothey A. EGFR antibodies in colorectal cancer: where do they belong? J Clin Oncol. 2010;28(31):4668-70.
95. Schaefer G, Haber L, Crocker LM, Shia S, Shao L, Dowbenko D, et al. A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies. Cancer Cell. 2011;20(4):472-86.
96. Chen Z, Xie W, Acheampong DO, Xu M, He H, Yang M, et al. A human IgG-like bispecific antibody co-targeting epidermal growth factor receptor and the vascular endothelial growth factor receptor 2 for enhanced antitumor activity. Cancer Biol Ther. 2016;17(2):139-50.
97. Schanzer JM, Wartha K, Moessner E, Hosse RJ, Moser S, Croasdale R, et al. XGFR∗, a novel affinity-matured bispecific antibody targeting IGF-1R and EGFR with combined signaling inhibition and enhanced immune activation for the treatment of pancreatic cancer. MAbs. 2016;8(4):811-27.
98. Chan JK, Hamilton CA, Cheung MK, Karimi M, Baker J, Gall JM, et al. Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study. Clin Cancer Res. 2006;12(6):1859-67.
99. Dorvillius M, Garambois V, Pourquier D, Gutowski M, Rouanet P, Mani JC, et al. Targeting of human breast cancer by a bispecific antibody directed against two tumour-associated antigens: ErbB-2 and carcinoembryonic antigen. Tumour Biol. 2002;23(6):337-47.
100. Oikawa S, Nakazato H, Kosaki G. Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence. Biochem Biophys Res Commun. 1987;142(2):511-8.
101. Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9(2):67-81.
102. Behr TM, Sharkey RM, Juweid MI, Dunn RM, Ying Z, Zhang CH, et al. Factors influencing the pharmacokinetics, dosimetry, and diagnostic accuracy of radioimmunodetection and radioimmunotherapy of carcinoembryonic antigen-expressing tumors. Cancer Res. 1996;56(8):1805-16.
103. Yamamoto M, Maehara Y, Sakaguchi Y, Mine H, Yamanaka T, Korenaga D, et al. Distributions in CEA doubling time differ in patients with recurrent colorectal carcinomas. Hepato-Gastroenterology. 2004;51(55):147-51.
104. Rother M. Carcinoembryonic antigen monitoring for early detection of asymptomatic incurable metastatic colorectal cancer. J Clin Oncol. 2007;25(10):1293-4. author reply 1294
105. Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313-27.
106. Osada T, Hsu D, Hammond S, Hobeika A, Devi G, Clay TM, et al. Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody. Br J Cancer. 2010;102(1):124-33.
107. Lutterbuese R, Raum T, Kischel R, Lutterbuese P, Schlereth B, Schaller E, et al. Potent control of tumor growth by CEA/CD3-bispecific single-chain antibody constructs that are not competitively inhibited by soluble CEA. J Immunother. 2009;32(4):341-52.
108. Behr TM, Sharkey RM, Juweid ME, Dunn RM, Ying Z, Zhang CH, et al. Variables influencing tumor dosimetry in radioimmunotherapy of CEA-expressing cancers with anti-CEA and antimucin monoclonal antibodies. J Nucl Med. 1997;38(3):409-18.
109. Dallas MR, Liu G, Chen WC, Thomas SN, Wirtz D, Huso DL, et al. Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis. FASEB J. 2012;26(6):2648-56.
110. Khare PD, Shao-Xi L, Kuroki M, Hirose Y, Arakawa F, Nakamura K, et al. Specifically targeted killing of carcinoembryonic antigen (CEA)-expressing cells by a retroviral vector displaying single-chain variable fragmented antibody to CEA and carrying the gene for inducible nitric oxide synthase. Cancer Res. 2001;61(1):370-5.
111. Oberst MD, Fuhrmann S, Mulgrew K, Amann M, Cheng L, Lutterbuese P, et al. CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas. MAbs. 2014;6(6):1571-84.
112. Peng L, Oberst MD, Huang J, Brohawn P, Morehouse C, Lekstrom K, et al. The CEA/CD3-bispecific antibody MEDI-565 (MT111) binds a nonlinear epitope in the full-length but not a short splice variant of CEA. PLoS One. 2012;7(5):e36412.
113. Pishvaian M, Morse MA, McDevitt J, Norton JD, Ren S, Robbie GJ, et al. Phase 1 dose escalation study of MEDI-565, a bispecific T-cell engager that targets human carcinoembryonic antigen, in patients with advanced gastrointestinal adenocarcinomas. Clin Colorectal Cancer. 2016;15(4):345-51.
114. Osada T, Patel SP, Hammond SA, Osada K, Morse MA, Lyerly HK. CEA/CD3-bispecific T cell-engaging (BiTE) antibody-mediated T lymphocyte cytotoxicity maximized by inhibition of both PD1 and PD-L1. Cancer Immunol Immunother. 2015;64(6):677-88.
115. Bacac M, Klein C, Umana P. CEA TCB: a novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors. Oncoimmunology. 2016;5(8):e1203498.
116. Bacac M, Fauti T, Sam J, Colombetti S, Weinzierl T, Ouaret D, et al. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. Clin Cancer Res. 2016;22(13):3286-97.
117. Lehmann S, Perera R, Grimm HP, Sam J, Colombetti S, Fauti T, et al. In vivo fluorescence imaging of the activity of CEA TCB, a novel T-cell bispecific antibody, reveals highly specific tumor targeting and fast induction of T-cell-mediated tumor killing. Clin Cancer Res. 2016;22(17):4417-27.
118. Dong B, Zhou C, He P, Li J, Chen S, Miao J, et al. A novel bispecific antibody, BiSS, with potent anti-cancer activities. Cancer Biol Ther. 2016;17(4):364-70.
119. Li J, Zhou C, Dong B, Zhong H, Chen S, Li Q, et al. Single domain antibody-based bispecific antibody induces potent specific anti-tumor activity. Cancer Biol Ther. 2016;17(12):1231-9.
120. Compte M, Alvarez-Cienfuegos A, Nunez-Prado N, Sainz-Pastor N, Blanco-Toribio A, Pescador N, et al. Functional comparison of single-chain and two-chain anti-CD3-based bispecific antibodies in gene immunotherapy applications. Oncoimmunology. 2014;3:e28810.
121. Molgaard K, Compte M, Nunez-Prado N, Harwood SL, Sanz L, Alvarez-Vallina L. Balanced secretion of anti-CEA x anti-CD3 diabody chains using the 2A self-cleaving peptide maximizes diabody assembly and tumor-specific cytotoxicity. Gene Ther. 2017;24:208.
122. Azria D, Larbouret C, Garambois V, Kramar A, Martineau P, Robert B, et al. Potentiation of ionising radiation by targeting tumour necrosis factor alpha using a bispecific antibody in human pancreatic cancer. Br J Cancer. 2003;89(10):1987-94.
123. Rauscher A, Frindel M, Rajerison H, Gouard S, Maurel C, Barbet J, et al. Improvement of the targeting of radiolabeled and functionalized liposomes with a two-step system using a bispecific monoclonal antibody (anti-CEA x anti-DTPA-in). Front Med (Lausanne). 2015;2:83.
124. Bodet-Milin C, Kraeber-Bodere F, Eugene T, Guerard F, Gaschet J, Bailly C, et al. Radioimmunotherapy for treatment of acute leukemia. Semin Nucl Med. 2016;46(2):135-46.
125. Mach JP, Pelegrin A, Buchegger F. Imaging and therapy with monoclonal antibodies in non-hematopoietic tumors. Curr Opin Immunol. 1991;3(5):685-93.
126. Goldenberg DM, Sharkey RM, Paganelli G, Barbet J, Chatal JF. Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy. J Clin Oncol. 2006;24(5):823-34.
127. Reilly RM. Radioimmunotherapy of solid tumors: the promise of pretargeting strategies using bispecific antibodies and radiolabeled haptens. J Nucl Med. 2006;47(2):196-9.
128. Sharkey RM, Rossi EA, McBride WJ, Chang CH, Goldenberg DM. Recombinant bispecific monoclonal antibodies prepared by the dock-and-lock strategy for pretargeted radioimmunotherapy. Semin Nucl Med. 2010;40(3):190-203.
129. Goldenberg DM, Rossi EA, Sharkey RM, McBride WJ, Chang CH. Multifunctional antibodies by the dock-and-lock method for improved cancer imaging and therapy by pretargeting. J Nucl Med. 2008;49(1):158-63.
130. van Schaijk FG, Oosterwijk E, Soede AC, Broekema M, Frielink C, McBride WJ, et al. Pretargeting of carcinoembryonic antigen-expressing tumors with a biologically produced bispecific anticarcinoembryonic antigen x anti-indium-labeled diethylenetriaminepentaacetic acid antibody. Clin Cancer Res. 2005;11(19 Pt 2):7130s-6s.
131. Yazaki PJ, Lee B, Channappa D, Cheung CW, Crow D, Chea J, et al. A series of anti-CEA/anti-DOTA bispecific antibody formats evaluated for pre-targeting: comparison of tumor uptake and blood clearance. Protein Eng Des Sel. 2013;26(3):187-93.
132. Karacay H, Brard PY, Sharkey RM, Chang CH, Rossi EA, McBride WJ, et al. Therapeutic advantage of pretargeted radioimmunotherapy using a recombinant bispecific antibody in a human colon cancer xenograft. Clin Cancer Res. 2005;11(21):7879-85.
133. Mirallie E, Sai-Maurel C, Faivre-Chauvet A, Regenet N, Chang CH, Goldenberg DM, et al. Improved pretargeted delivery of radiolabelled hapten to human tumour xenograft in mice by avidin chase of circulating bispecific antibody. Eur J Nucl Med Mol Imaging. 2005;32(8):901-9.
134. Kraeber-Bodere F, Rousseau C, Bodet-Milin C, Ferrer L, Faivre-Chauvet A, Campion L, et al. Targeting, toxicity, and efficacy of 2-step, pretargeted radioimmunotherapy using a chimeric bispecific antibody and 131I-labeled bivalent hapten in a phase I optimization clinical trial. J Nucl Med. 2006;47(2):247-55.
135. Salaun PY, Campion L, Bournaud C, Faivre-Chauvet A, Vuillez JP, Taieb D, et al. Phase II trial of anticarcinoembryonic antigen pretargeted radioimmunotherapy in progressive metastatic medullary thyroid carcinoma: biomarker response and survival improvement. J Nucl Med. 2012;53(8):1185-92.
136. Bodet-Milin C, Ferrer L, Rauscher A, Masson D, Rbah-Vidal L, Faivre-Chauvet A, et al. Pharmacokinetics and dosimetry studies for optimization of pretargeted radioimmunotherapy in CEA-expressing advanced lung cancer patients. Front Med (Lausanne). 2015;2:84.
137. Schoffelen R, Sharkey RM, Goldenberg DM, Franssen G, McBride WJ, Rossi EA, et al. Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts. Mol Cancer Ther. 2010;9(4):1019-27.
138. McBride WJ, Zanzonico P, Sharkey RM, Noren C, Karacay H, Rossi EA, et al. Bispecific antibody pretargeting PET (immunoPET) with an 124I-labeled hapten-peptide. J Nucl Med. 2006;47(10):1678-88.
139. Hall H, Velikyan I, Blom E, Ulin J, Monazzam A, Pahlman L, et al. In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and (67/68Ga)-labeled haptens by pretargeting. Am J Nucl Med Mol Imaging. 2012;2(2):141-50.
140. Sharkey RM, Karacay H, Vallabhajosula S, McBride WJ, Rossi EA, Chang CH, et al. Metastatic human colonic carcinoma: molecular imaging with pretargeted SPECT and PET in a mouse model. Radiology. 2008;246(2):497-507.
141. Sharkey RM, Cardillo TM, Rossi EA, Chang CH, Karacay H, McBride WJ, et al. Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibody. Nat Med. 2005;11(11):1250-5.
142. Aarts F, Boerman OC, Sharkey RM, Hendriks T, Chang CH, McBride WJ, et al. Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab')2 antibody. Cancer. 2010;116(4 Suppl):1111-7.
143. Bodet-Milin C, Faivre-Chauvet A, Carlier T, Rauscher A, Bourgeois M, Cerato E, et al. Immuno-PET using anticarcinoembryonic antigen bispecific antibody and 68Ga-labeled peptide in metastatic medullary thyroid carcinoma: clinical optimization of the pretargeting parameters in a first-in-human trial. J Nucl Med. 2016;57(10):1505-11.
144. Rajasekaran AK, Anilkumar G, Christiansen JJ. Is prostate-specific membrane antigen a multifunctional protein? Am J Physiol Cell Physiol. 2005;288(5):C975-81.
145. Cardillo MR, Gentile V, Di Silverio F. Correspondence re: Ghosh A and Heston WDW. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;93(4):641-43.
146. Caromile LA, Dortche K, Rahman MM, Grant CL, Stoddard C, Ferrer FA, et al.PSMA redirects cell survival signaling from the MAPK to the PI3K-AKT pathways to promote the progression of prostate cancer. Sci Signal. 2017;10(470).
147. Kiess AP, Banerjee SR, Mease RC, Rowe SP, Rao A, Foss CA, et al. Prostate-specific membrane antigen as a target for cancer imaging and therapy. Q J Nucl Med Mol Imaging. 2015;59(3):241-68.
148. Friedrich M, Raum T, Lutterbuese R, Voelkel M, Deegen P, Rau D, et al. Regression of human prostate cancer xenografts in mice by AMG 212/BAY2010112, a novel PSMA/CD3-Bispecific BiTE antibody cross-reactive with non-human primate antigens. Mol Cancer Ther. 2012;11(12):2664-73.
149. Hernandez-Hoyos G, Sewell T, Bader R, Bannink J, Chenault RA, Daugherty M, et al. MOR209/ES414, a novel bispecific antibody targeting PSMA for the treatment of metastatic castration-resistant prostate cancer. Mol Cancer Ther. 2016;15(9):2155-65.
150. Baum V, Buhler P, Gierschner D, Herchenbach D, Fiala GJ, Schamel WW, et al. Antitumor activities of PSMAxCD3 diabodies by redirected T-cell lysis of prostate cancer cells. Immunotherapy. 2013;5(1):27-38.
151. Buhler P, Wolf P, Gierschner D, Schaber I, Katzenwadel A, Schultze-Seemann W, et al. A bispecific diabody directed against prostate-specific membrane antigen and CD3 induces T-cell mediated lysis of prostate cancer cells. Cancer Immunol Immunother. 2008;57(1):43-52.
152. Buhler P, Molnar E, Dopfer EP, Wolf P, Gierschner D, Wetterauer U, et al. Target-dependent T-cell activation by coligation with a PSMA x CD3 diabody induces lysis of prostate cancer cells. J Immunother. 2009;32(6):565-73.
153. Fortmuller K, Alt K, Gierschner D, Wolf P, Baum V, Freudenberg N, et al. Effective targeting of prostate cancer by lymphocytes redirected by a PSMA x CD3 bispecific single-chain diabody. Prostate. 2011;71(6):588-96.
154. Muller D, Karle A, Meissburger B, Hofig I, Stork R, Kontermann RE. Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. J Biol Chem. 2007;282(17):12650-60.
155. Trivedi A, Stienen S, Zhu M, Li H, Yuraszeck T, Gibbs J, et al. Clinical pharmacology and translational aspects of bispecific antibodies. Clin Transl Sci. 2017;10(3):147-62.