Development of Cancer Vaccines Targeting Brachyury, a Transcription Factor Associated with Tumor Epithelial-Mesenchymal Transition

Cells Tissues Organs

Volumn 203, Issue 2, 2017, Pages 128-138

  Hamilton, Duane H ^a   David, Justin M ^a   Dominguez, Charli ^a   Palena, Claudia ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Brachyury; Cancer vaccines; Epithelial mesenchymal transition; Immune resistance

Indexed keywords

CANCER VACCINE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR BRACHYURY; TUMOR ANTIGEN; UNCLASSIFIED DRUG; BRACHYURY PROTEIN; FETOPROTEIN; T BOX TRANSCRIPTION FACTOR;

ADENOVIRIDAE; CANCER PROGNOSIS; CANCER RESISTANCE; CONFERENCE PAPER; CYTOTOXICITY; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; IN VIVO STUDY; NONHUMAN; POXVIRIDAE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; SACCHAROMYCES CEREVISIAE; TUMOR ESCAPE; ANIMAL; DRUG RESISTANCE; IMMUNOLOGY; IMMUNOTHERAPY; NEOPLASM; PATHOLOGY;

ANIMALS; CANCER VACCINES; DRUG RESISTANCE, NEOPLASM; EPITHELIAL-MESENCHYMAL TRANSITION; FETAL PROTEINS; HUMANS; IMMUNOTHERAPY; NEOPLASMS; T-BOX DOMAIN PROTEINS;

EID: 85013819324     PISSN: 14226405     EISSN: 14226421     Source Type: Journal    
DOI: 10.1159/000446495     Document Type: Conference Paper

References (70)

1. Akalay, I., B. Janji, M. Hasmim, M.Z. Noman, F. Andre, P. De Cremoux, P. Bertheau, C. Badoual, P. Vielh, A.K. Larsen, M. Sabbah, T.Z. Tan, J.H. Keira, N.T. Hung, J.P. Thiery, F. Mami-Chouaib, S. Chouaib (2013a) Epithelialto-mesenchymal transition and autophagy induction in breast carcinoma promote escape from T-cell-mediated lysis. Cancer Res 73: 2418-2427.
2. Akalay, I., B. Janji, M. Hasmim, M.Z. Noman, J.P. Thiery, F. Mami-Chouaib, S. Chouaib (2013b) EMT impairs breast carcinoma cell susceptibility to CTL-mediated lysis through autophagy induction. Autophagy 9: 1104-1106.
3. Barresi, V., A. Ieni, G. Branca, G. Tuccari (2014) Brachyury: A diagnostic marker for the differential diagnosis of chordoma and hemangioblastoma versus neoplastic histological mimickers. Dis Markers 2014: 514753.
4. Barresi, V., E. Vitarelli, G. Branca, M. Antonelli, F. Giangaspero, G. Barresi (2012) Expression of brachyury in hemangioblastoma: potential use in differential diagnosis. Am J Surg Pathol 36: 1052-1057.
5. Bilusic, M., C.R. Heery, P.M. Arlen, M. Rauckhorst, D. Apelian, K.Y. Tsang, J.A. Tucker, C. Jochems, J. Schlom, J.L. Gulley, R.A. Madan (2014) Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol Immunother 63: 225-234.
6. Borghaei, H., L. Paz-Ares, L. Horn, D.R. Spigel, M. Steins, N.E. Ready, L.Q. Chow, E.E. Vokes, E. Felip, E. Holgado, F. Barlesi, M. Kohlhaufl, O. Arrieta, M.A. Burgio, J. Fayette, H. Lena, E. Poddubskaya, D.E. Gerber, S.N. Gettinger, C.M. Rudin, N. Rizvi, L. Crino, G.R. Blumenschein, Jr., S.J. Antonia, C. Dorange, C.T. Harbison, F. Graf Finckenstein, J.R. Brahmer (2015) Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373: 1627-1639.
7. Byers, L.A., L. Diao, J. Wang, P. Saintigny, L. Girard, M. Peyton, et al. (2013) An epithelialmesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res 19 : 279-290.
8. Chaft, J.E., A. Litvak, M.E. Arcila, P. Patel, S.P. DAngelo, L.M. Krug, V. Rusch, A. Mattson, C. Coeshott, B. Park, D.M. Apelian, M.G. Kris, C.G. Azzoli (2014) Phase II study of the GI-4000 KRAS vaccine after curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, or G12V mutation. Clin Lung Cancer 15: 405-410.
9. Creighton, C.J., X. Li, M. Landis, J.M. Dixon, V.M. Neumeister, A. Sjolund, D.L. Rimm, H. Wong, A. Rodriguez, J.I. Herschkowitz, C. Fan, X. Zhang, X. He, A. Pavlick, M.C. Gutierrez, L. Renshaw, A.A. Larionov, D. Faratian, S.G. Hilsenbeck, C.M. Perou, M.T. Lewis, J.M. Rosen, J.C. Chang (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 106: 13820-13825.
10. Do, K., D. Wilsker, J. Ji, J. Zlott, T. Freshwater, R.J. Kinders, J. Collins, A.P. Chen, J.H. Doroshow, S. Kummar (2015) Phase I study of single-Agent AZD1775 (MK-1775), a Wee1 kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol 33: 3409-3415.
11. Du, R., S. Wu, X. Lv, H. Fang, S. Wu, J. Kang (2014) Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma. J Exp Clin Cancer Res 33: 105.
12. Edwards, Y.H., W. Putt, K.M. Lekoape, D. Stott, M. Fox, D.A. Hopkinson, J. Sowden (1996) The human homolog T of the mouse T(Brachyury) gene; gene structure, cDNA sequence, and assignment to chromosome 6q27. Genome Res 6: 226-233.
13. Fernando, R.I., M.D. Castillo, M. Litzinger, D.H. Hamilton, C. Palena (2011) IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells. Cancer Res 71: 5296-5306.
14. Fernando, R.I., M. Litzinger, P. Trono, D.H. Hamilton, J. Schlom, C. Palena (2010) The Tbox transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. J Clin Invest 120: 533-544.
15. Gabitzsch, E.S., K.Y. Tsang, C. Palena, J.M. David, M. Fantini, A. Kwilas, A.E. Rice, Y. Latchman, J.W. Hodge, J.L. Gulley, R.A. Madan, C.R. Heery, J.P. Balint Jr., F.R. Jones, J. Schlom (2015) The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic. Oncotarget 6: 31344-31359.
16. Gabitzsch, E.S., Y. Xu, J.P. Balint, Jr., Z.C. Hartman, H.K. Lyerly, F.R. Jones (2010) Anti-Tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA. Cancer Immunol Immunother 59: 1131-1135.
17. Gabitzsch, E.S., Y. Xu, L.H. Yoshida, J. Balint, R.B. Gayle, A. Amalfitano, F.R. Jones (2009) A preliminary and comparative evaluation of a novel Ad5 [E1-, E2b-] recombinant-based vaccine used to induce cell mediated immune responses. Immunol Lett 122: 44-51.
18. Garon, E.B., N.A. Rizvi, R. Hui, N. Leighl, A.S. Balmanoukian, J.P. Eder, A. Patnaik, C. Aggarwal, M. Gubens, L. Horn, E. Carcereny, M.J. Ahn, E. Felip, J.S. Lee, M. D. Hellmann, O. Hamid, J.W. Goldman, J.C. Soria, M. Dolled-Filhart, R.Z. Rutledge, J. Zhang, J.K. Lunceford, R. Rangwala, G.M. Lubiniecki, C. Roach, K. Emancipator, L. Gandhi (2015) Pembrolizumab for the treatment of nonsmall-cell lung cancer. N Engl J Med 372: 2018-2028.
19. Hamilton, D.H., R.I. Fernando, J. Schlom, C. Palena (2015) Aberrant expression of the embryonic transcription factor brachyury in human tumors detected with a novel rabbit monoclonal antibody. Oncotarget 6: 4853-4862.
20. Hamilton, D.H., B. Huang, R.I. Fernando, K.Y. Tsang, C. Palena (2014) WEE1 inhibition alleviates resistance to immune attack of tumor cells undergoing epithelial-mesenchymal transition. Cancer Res 74: 2510-2519.
21. Hamilton, D.H., M. T. Litzinger, A. Jales, B. Huang, R.I. Fernando, J.W. Hodge, A. Ardiani, D. Apelian, J. Schlom, C. Palena (2013) Immunological targeting of tumor cells undergoing an epithelial-mesenchymal transition via a recombinant brachyury-yeast vaccine. Oncotarget 4: 1777-1790.
22. Hanahan, D., R.A. Weinberg (2011) Hallmarks of cancer: The next generation. Cell 144: 646-674.
23. Haro, A., T. Yano, M. Kohno, T. Yoshida, T. Koga, T. Okamoto, M. Takenoyama, Y. Maehara (2013) Expression of Brachyury gene is a significant prognostic factor for primary lung carcinoma. Ann Surg Oncol 20(suppl 3): S509-S516.
24. Heery, C.R., B.H. Singh, M. Rauckhorst, J.L. Marte, R.N. Donahue, I. Grenga, T.C. Rodell, W. Dahut, P.M. Arlen, R.A. Madan, J. Schlom, J.L. Gulley (2015) Phase I trial of a yeast-based therapeutic cancer vaccine (GI-6301) targeting the transcription factor brachyury. Cancer Immunol Res 3: 1248-1256.
25. Herrmann, B.G., S. Labeit, A. Poustka, T.R. King, H. Lehrach (1990) Cloning of the T gene required in mesoderm formation in the mouse. Nature 343: 617-622.
26. Huang, B., J.R. Cohen, R.I. Fernando, D.H. Hamilton, M. T. Litzinger, J.W. Hodge, C. Palena (2013) The embryonic transcription factor Brachyury blocks cell cycle progression and mediates tumor resistance to conventional antitumor therapies. Cell Death Dis 4: e682.
27. Imajyo, I., T. Sugiura, Y. Kobayashi, M. Shimoda, K. Ishii, N. Akimoto, N. Yoshihama, I. Kobayashi, Y. Mori (2012) T-box transcription factor Brachyury expression is correlated with epithelial-mesenchymal transition and lymph node metastasis in oral squamous cell carcinoma. Int J Oncol 41: 1985-1995.
28. Kalluri, R., R.A. Weinberg (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119: 1420-1428.
29. Kilic, N., S. Feldhaus, E. Kilic, P. Tennstedt, D. Wicklein, R. Wasielewski, C. Viebahn, H. Kreipe, U. Schumacher (2011) Brachyury expression predicts poor prognosis at early stages of colorectal cancer. Eur J Cancer 47: 1080-1085.
30. Kim, H.P., S.W. Han, S.H. Song, E.G. Jeong, M.Y. Lee, D. Hwang, S.A. Im, Y.J. Bang, T.Y. Kim (2014) Testican-1-mediated epithelial-mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer. Oncogene 33: 3334-3341.
31. Kispert, A., B.G. Herrmann (1993) The Brachyury gene encodes a novel DNA binding protein. EMBO J 12: 3211-3220.
32. Kispert, A., B. Koschorz, B.G. Herrmann (1995) The T protein encoded by Brachyury is a tissue-specific transcription factor. EMBO J 14: 4763-4772.
33. Kudo-Saito, C., H. Shirako, T. Takeuchi, Y. Kawakami (2009) Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell 15: 195-206.
34. Kurrey, N.K., S.P. Jalgaonkar, A.V. Joglekar, A.D. Ghanate, P.D. Chaskar, R.Y. Doiphode, S.A. Bapat (2009) Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells 27: 2059-2068.
35. Larocca, C., J.R. Cohen, R.I. Fernando, B. Huang, D.H. Hamilton, C. Palena (2013) An autocrine loop between TGF-β1 and the transcription factor brachyury controls the transition of human carcinoma cells into a mesenchymal phenotype. Mol Cancer Ther 12: 1805-1815.
36. Madan, R.A., M. Bilusic, C. Heery, J. Schlom, J.L. Gulley (2012) Clinical evaluation of TRICOM vector therapeutic cancer vaccines. Semin Oncol 39: 296-304.
37. Madan, R. A., M. Mohebtash, P.M. Arlen, M. Vergati, M. Rauckhorst, S.M. Steinberg, K. Y. Tsang, D.J. Poole, H.L. Parnes, J.J. Wright, W.L. Dahut, J. Schlom, J.L. Gulley (2012) Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: A phase 1 doseescalation trial. Lancet Oncol 13: 501-508.
38. Mayr, A., K. Danner (1978) Vaccination against pox diseases under immunosuppressive conditions. Dev Biol Stand 41: 225-234.
39. Miettinen, M., Z. Wang, J. Lasota, C. Heery, J. Schlom, C. Palena (2015) Nuclear brachyury expression is consistent in chordoma, common in germ cell tumors and small cell carcinomas, and rare in other carcinomas and sarcomas: An immunohistochemical study of 5, 229 cases. Am J Surg Pathol 39: 1305-1312.
40. Ottaviano, Y., L. Gerace (1985) Phosphorylation of the nuclear lamins during interphase and mitosis. J Biol Chem 260: 624-632.
41. Palena, C., R. I. Fernando, D. H. Hamilton (2014) An immunotherapeutic intervention against tumor progression: Targeting a driver of the epithelial-To-mesenchymal transition. Oncoimmunology 3: e27220.
42. Palena, C., D.E. Polev, K.Y. Tsang, R.I. Fernando, M. Litzinger, L.L. Krukovskaya, A.V. Baranova, A.P. Kozlov, J. Schlom (2007) The human T-box mesodermal transcription factor Brachyury is a candidate target for T-cell-mediated cancer immunotherapy. Clin Cancer Res 13: 2471-2478.
43. Palena, C., M. Roselli, M.T. Litzinger, P. Ferroni, L. Costarelli, A. Spila, F. Cavaliere, B. Huang, R.I. Fernando, D.H. Hamilton, C. Jochems, K.Y. Tsang, Q. Cheng, H. Kim Lyerly, J. Schlom, F. Guadagni (2014) Overexpression of the EMT driver brachyury in breast carcinomas: Association with poor prognosis. J Natl Cancer Inst 106: dju054.
44. Palena, C., J. Schlom (2010) Vaccines against human carcinomas: strategies to improve antitumor immune responses. J Biomed Biotechnol 2010: 380697.
45. Pinto, F., N.C. Campanella, L.F. Abrahao-Machado, C. Scapulatempo-Neto, A.T. de Oliveira, M.J. Brito, R.P. Andrade, D.P. Guimaraes, R.M. Reis (2015) The embryonic Brachyury transcription factor is a novel biomarker of GIST aggressiveness and poor survival. Gastric Cancer 19: 651-659.
46. Pinto, F., N. Pertega-Gomes, M.S. Pereira, J.R. Vizcaino, P. Monteiro, R.M. Henrique, F. Baltazar, R.P. Andrade, R.M. Reis (2014) Tbox transcription factor Brachyury is associated with prostate cancer progression and aggressiveness. Clin Cancer Res 20: 4949-4961.
47. Powles, T., J.P. Eder, G.D. Fine, F.S. Braiteh, Y. Loriot, C. Cruz, J. Bellmunt, H.A. Burris, D.P. Petrylak, S.L. Teng, X. Shen, Z. Boyd, P.S. Hegde, D.S. Chen, N.J. Vogelzang (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515: 558-562.
48. Rajeshkumar, N.V., E. De Oliveira, N. Ottenhof, J. Watters, D. Brooks, T. Demuth, S.D. Shumway, S. Mizuarai, H. Hirai, A. Maitra, M. Hidalgo (2011) MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. Clin Cancer Res 17: 2799-2806.
49. Ribas, A. (2015) Adaptive immune resistance: how cancer protects from immune attack. Cancer Discov 5: 915-919.
50. Roselli, M., R.I. Fernando, F. Guadagni, A. Spila, J. Alessandroni, R. Palmirotta, L. Costarelli, M. Litzinger, D. Hamilton, B. Huang, J. Tucker, K.Y. Tsang, J. Schlom, C. Palena (2012) Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: An opportunity for novel interventions against lung cancer. Clin Cancer Res 18: 3868-3879.
51. Schlom, J., J.W. Hodge, C. Palena, K.Y. Tsang, C. Jochems, J.W. Greiner, B. Farsaci, R.A. Madan, C.R. Heery, J.L. Gulley (2014) Therapeutic cancer vaccines. Adv Cancer Res 121: 67-124.
52. Shao, C., J. Zhang, J. Fu, F. Ling (2015) The potential role of Brachyury in inducing epithelial-To-mesenchymal transition (EMT) and HIF-1α expression in breast cancer cells. Biochem Biophys Res Commun 467: 1083-1089.
53. Shin, D. S., A. Ribas (2015) The evolution of checkpoint blockade as a cancer therapy: whats here, whats next? Curr Opin Immunol 33C: 23-35.
54. Tan, T.Z., Q.H. Miow, Y. Miki, T. Noda, S. Mori, R.Y. Huang, J.P. Thiery (2014) Epithelialmesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med 6: 1279-1293.
55. Tang, X., L. Jing, J. Chen (2012) Changes in the molecular phenotype of nucleus pulposus cells with intervertebral disc aging. PLoS One 7: e52020.
56. Thiery, J.P. (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2: 442-454.
57. Thiery, J.P. (2003) Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol 15: 740-746.
58. Thomson, S., E. Buck, F. Petti, G. Griffin, E. Brown, N. Ramnarine, K.K. Iwata, N. Gibson, J.D. Haley (2005) Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 65: 9455-9462.
59. Thomson, S., F. Petti, I. Sujka-Kwok, D. Epstein, J.D. Haley (2008) Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy. Clin Exp Metastasis 25: 843-854.
60. Tirabosco, R., D.C. Mangham, A.E. Rosenberg, S. Vujovic, K. Bousdras, S. Pizzolitto, G. De Maglio, M.A. den Bakker, L. Di Francesco, R.K. Kalil, N.A. Athanasou, P. ODonnell, E.F. McCarthy, A.M. Flanagan (2008) Brachyury expression in extra-Axial skeletal and soft tissue chordomas: A marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Am J Surg Pathol 32: 572-580.
61. Topalian, S.L., M. Sznol, D.F. McDermott, H.M. Kluger, R.D. Carvajal, W.H. Sharfman, J.R. Brahmer, D.P. Lawrence, M.B. Atkins, J.D. Powderly, P.D. Leming, E.J. Lipson, I. Puzanov, D.C. Smith, J.M. Taube, J.M. Wigginton, G.D. Kollia, A. Gupta, D. M. Pardoll, J.A. Sosman, F.S. Hodi (2014) Survival, durable tumor remission, and long-Term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32: 1020-1030.
62. Tucker, J.A., C. Jochems, B. Boyerinas, J. Fallon, J.W. Greiner, C. Palena, T.C. Rodell, J. Schlom, K.Y. Tsang (2014) Identification and characterization of a cytotoxic T-lymphocyte agonist epitope of brachyury, a transcription factor involved in epithelial to mesenchymal transition and metastasis. Cancer Immunol Immunother 63: 1307-1317.
63. Vega, S., A.V. Morales, O.H. Ocana, F. Valdes, I. Fabregat, M.A. Nieto (2004) Snail blocks the cell cycle and confers resistance to cell death. Genes Dev 18: 1131-1143.
64. Vujovic, S., S. Henderson, N. Presneau, E. Odell, T.S. Jacques, R. Tirabosco, C. Boshoff, A.M. Flanagan (2006) Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol 209: 157-165.
65. Whiteside, T.L. (2009) Tricks tumors use to escape from immune control. Oral Oncol 45: e119-123.
66. Wilkinson, D.G., S. Bhatt, B.G. Herrmann (1990) Expression pattern of the mouse T gene and its role in mesoderm formation. Nature 343: 657-659.
67. Xu, K., B. Liu, Y. Liu (2015) Impact of Brachyury on epithelial-mesenchymal transitions and chemosensitivity in non-small cell lung cancer. Mol Med Rep 12: 995-1001.
68. Yang, X.R., D. Ng, D.A. Alcorta, N.J. Liebsch, E. Sheridan, S. Li, A.M. Goldstein, D.M. Parry, M.J. Kelley (2009) T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet 41: 1176-1178.
69. Yu, M., A. Bardia, B.S. Wittner, S.L. Stott, M.E. Smas, D.T. Ting, S.J. Isakoff, J.C. Ciciliano, M.N. Wells, A.M. Shah, K.F. Concannon, M.C. Donaldson, L.V. Sequist, E. Brachtel, D. Sgroi, J. Baselga, S. Ramaswamy, M. Toner, D.A. Haber, S. Maheswaran (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339: 580-584.
70. Zitvogel, L., A. Tesniere, G. Kroemer (2006) Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6: 715-727.