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Biochemistry (Moscow)

, Volume 84, Issue 7, pp 773–781 | Cite as

MUC1 in Cancer Immunotherapy — New Hope or Phantom Menace?

  • M. S. SyrkinaEmail author
  • M. A. RubtsovEmail author
Mini-Review
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Abstract

Understanding of the functioning of MUC1 (human mucin) has advanced significantly over 40 years of its investigation. The anti-adhesive properties of the extracellular domain, which were the main focus of early studies initially explaining overexpression of MUC1 in progressing oncological diseases, were gradually put on the back burner. Researchers became more interested in its regulatory and signaling functions in cells rather in its anti-adhesive properties. The found the ability of MUC1 for signal transduction, and its ability to participate in cell metabolism opened new possibilities for improved control over cancer cells in addition to just attracting antigens of the immune system to a target. Nevertheless, there are issues in the functioning of MUC1 that raise doubts about its effectiveness in cancer immunotherapy.

Keywords

mucin MUC1 immunotherapy glycosylation immunosuppression tandem repeats CAR-T 

Abbreviations

APC

antigen-presenting cell

CAR-T

T-lymphocyte carrying chimeric antigen receptor

MHC

major histocompatibility complex

MUC1

human mucin

MUC1-C

C-terminal (cytoplasmic) MUC1 subunit

MUC1-N

N-terminal (extracellular) MUC1 subunit

TCR

T-cell receptor

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References

  1. 1.
    Jerome, K. R., Barnd, D. L., Bendt, K. M., Boyer, C. M., Taylor-Papadimitriou, J., McKenzie, I. F., Bast, R. C., Jr., and Finn, O. J. (1991) Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells, Cancer Res., 51, 2908–2916.Google Scholar
  2. 2.
    Berd, D., Maguire, H. C., Jr., McCue, P., and Mastrangelo, M. J. (1990) Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients, J. Clin. Oncol., 8, 1858–1867; doi: 10.1200/JCO.1990.8.11.1858.CrossRefGoogle Scholar
  3. 3.
    Ioannides, C. G., Fisk, B., Jerome, K. R., Irimura, T., Wharton, J. T., and Finn, O. J. (1993) Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides, J. Immunol., 151, 3693–3703.Google Scholar
  4. 4.
    Apostolopoulos, V., Pietersz, G. A., and McKenzie, I. F. (1999) MUC1 and breast cancer, Curr. Opin. Mol. Ther., 1, 98–103.Google Scholar
  5. 5.
    Taylor-Papadimitriou, J., Burchell, J., Miles, D. W., and Dalziel, M. (1999) MUC1 and cancer, Biochim. Biophys. Acta, 1455, 301–313; doi: 10.1016/S0925-4439(99)00055-1.CrossRefGoogle Scholar
  6. 6.
    Ho, S. B., Niehans, G. A., Lyftogt, C., Yan, P. S., Cherwitz, D. L., Gum, E. T., Dahiya, R., and Kim, Y. S. (1993) Heterogeneity of mucin gene expression in normal and neoplastic tissues, Cancer Res., 53, 641–651.Google Scholar
  7. 7.
    Hull, S. R., Bright, A., Carraway, K. L., Abe, M., Hayes, D. F., and Kufe, D. W. (1989) Oligosaccharide differences in the DF3 sialomucin antigen from normal human milk and the BT-20 human breast carcinoma cell line, Cancer Commun., 1, 261–267.Google Scholar
  8. 8.
    Brockhausen, I., Yang, J. M., Burchell, J., Whitehouse, C., and Taylor-Papadimitriou, J. (1995) Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer cells, FEBS J., 233, 607–617; doi: 10.1111/j.1432-1033.1995.607_2.x.Google Scholar
  9. 9.
    Lloyd, K. O., Burchell, J., Kudryashov, V., Yin, B. W., and Taylor-Papadimitriou, J. (1996) Comparison of O-linked carbohydrate chains in MUC-1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines. Demonstration of simpler and fewer glycan chains in tumor cells, J. Biol. Chem., 271, 33325–33334; doi: 10.1074/jbc.271.52.33325.CrossRefGoogle Scholar
  10. 10.
    Burdick, M. D., Harris, A., Reid, C. J., Iwamura, T., and Hollingsworth, M. A. (1997) Oligosaccharides expressed on MUC1 produced by pancreatic and colon tumor cell lines, J. Biol. Chem., 272, 24198–24202; doi: 10.1074/jbc.272. 39.24198.CrossRefGoogle Scholar
  11. 11.
    Heyderman, E., Steele, K., and Ormerod, M. G. (1979) A new antigen on the epithelial membrane: its immunoperox-idase localization in normal and neoplastic tissue, J. Clin. Pathol., 32, 35–39.CrossRefGoogle Scholar
  12. 12.
    Price, M. R., and Tendler, S. J. B. (1993) Polymorphic epithelial mucins (PEM): molecular characteristics and association with breast cancer, Breast, 2, 3–7; doi: 10.1016/0960-9776(93)90028-E.CrossRefGoogle Scholar
  13. 13.
    Apostolopoulos, V., Chelvanayagam, G., Xing, P. X., and McKenzie, I. F. C. (1998) Anti-MUC1 antibodies react directly with MUC1 peptides presented by class I H2 and HLA molecules, J. Immunol., 161, 767–775.Google Scholar
  14. 14.
    Davies, G. M., Bosze, S., Hudecz, F., Price, M. R., and Tendler, S. J. (1994) Characterization of a recombinant Fv fragment of anti-MUC1 antibody HMFG1, Cancer Lett., 82, 179–184; doi: 10.1016/0304-3835(94)90009-4.CrossRefGoogle Scholar
  15. 15.
    Ordonez, N. G. (1997) The value of antibodies 44-3A6, SM3, HBME-1, and thrombomodulin in differentiating epithelial pleural mesothelioma from lung adenocarcino-ma: a comparative study with other commonly used antibodies, Am. J. Surg. Pathol., 21, 1399–1408.CrossRefGoogle Scholar
  16. 16.
    Price, M., Petrakou, E., Sekowski, M., and Murray, A. (1997) Immunogenicity of the hydrophilic region of the MUC1 mucin protein core, Oncol. Rep., 4, 337–339; doi: 0.3892/or.4.2.337.Google Scholar
  17. 17.
    Denton, G., Brady, K., Lo, B. K., Murray, A., Rosamund, C., Graves, L., Hughes, O. D., Tendler, S. J., Laughton, C. A., and Price, M. R. (1999) Production and characterization of an anti-(MUC1 mucin) recombinant diabody, Cancer Immun. Immunother., 48, 29–38; doi: 10.1007/s002620050545.CrossRefGoogle Scholar
  18. 18.
    Murray, A., Sekowski, M., Spencer, D. I., Denton, G., and Price, M. R. (1997) Purification of monoclonal antibodies by epitope and mimotope affinity chromatography, J. Chromatogr. A, 782, 49–54; doi: 10.1016/S0021-9673(97)00674-2.CrossRefGoogle Scholar
  19. 19.
    Petrakou, E., Murray, A., and Price, M. R. (1998) Epitope mapping of anti-MUC1 mucin protein core monoclonal antibodies, Tumour Biol., 19, Suppl. 1, 21–29.Google Scholar
  20. 20.
    Xing, P. X., Prenzoska, J., and McKenzie, I. F. (1992) Epitope mapping of anti-breast and anti-ovarian mucin monoclonal antibodies, Mol. Immunol., 29, 641–650; doi: 10.1016/0161-5890(92)90201-8.CrossRefGoogle Scholar
  21. 21.
    Taylor-Papadimitriou, J., Peterson, J. A., Arklie, J., Burchell, J., Ceriani, R. L., and Bodmer, W. F. (1981) Monoclonal antibodies to epithelium-specific components of the human milk fat globule membrane: production and reaction with cells in culture, Int. J. Cancer, 15, 17–21.CrossRefGoogle Scholar
  22. 22.
    Epenetos, A. A., Canti, G., Taylor-Papadimitriou, J., Curling, M., and Bodmer, W. F. (1982) Use of two epithelium-specific monoclonal antibodies for diagnosis of malignancy in serous effusions, Lancet, 2, 1004–1006; doi: 10.1016/S0140-6736(82)90047-2.CrossRefGoogle Scholar
  23. 23.
    Granowska, M., Mather, S. J., Jobling, T., Naeem, M., Burchell, J., Taylor-Papadimitriou, J., Shepherd, J., and Britton, K. E. (1990) Radiolabeled stripped mucin, SM3, monoclonal antibody for immunoscintigraphy of ovarian tumors, Int. J. Biol. Markers, 5, 89–96; doi: 10.1177/172460089000500208.CrossRefGoogle Scholar
  24. 24.
    Price, M. R., Pugh, J. A., Hudecz, F., Griffiths, W., Jacobs, E., Symonds, I. M., Clarke, A. J., Chan, W. C., and Baldwin, R. W. (1990) C595 - a monoclonal antibody against the protein core of human urinary epithelial mucin commonly expressed in breast carcinomas, Br. J. Cancer, 61, 681–686; doi: 10.1038/bjc.1990.154.CrossRefGoogle Scholar
  25. 25.
    Xing, P. X., Apostolopoulos, V., Pietersz, G., and McKenzie, I. F. (2001) Anti-mucin monoclonal antibodies, Front. Biosci., 6, D1284-D1295.Google Scholar
  26. 26.
    Burchell, J., and Taylor-Papadimitriou, J. (1993) Effect of modification of carbohydrate side chains on the reactivity of antibodies with core-protein epitopes of the MUC1 gene product, Epithelial Cell Biol., 2, 155–162.Google Scholar
  27. 27.
    Von Mensdorff-Pouilly, S., Petrakou, E., Kenemans, P., van Uffelen, K., Verstraeten, A. A., Snijdewint, F. G., van Kamp, G. J., Schol, D. J., Reis, C. A., Price, M. R., Livingston, P. O., and Hilgers, J. (2000) Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and N-acetylgalactosamine (GalNAc) peptides, Int. J. Cancer, 86, 702–712.CrossRefGoogle Scholar
  28. 28.
    Karsten, U., von Mensdorff-Pouilly, S., and Goletz, S. (2005) What makes MUC1 a tumor antigen? Tumour Biol., 26, 217–220; doi: 10.1159/000086956.CrossRefGoogle Scholar
  29. 29.
    Grinstead, J. S., Koganty, R. R., Krantz, M. J., Longenecker, B. M., and Campbell, A. P. (2002) Effect of glycosylation on MUC1 humoral immune recognition: NMR studies of MUC1 glycopeptide-antibody interactions, Biochemistry, 41, 9946–9961; doi: 10.1021/bi012176z.CrossRefGoogle Scholar
  30. 30.
    Dohi, D. F., Sutton, R. C., Frazier, M. L., Nakamori, S., McIsaac, A. M., and Irimura, T. (1993) Regulation of sialo-mucin production in colon carcinoma cells, J. Biol. Chem., 268, 10133–10138.Google Scholar
  31. 31.
    Lakshminarayanan, V., Thompson, P., Wolfert, M. A., Buskas, T., Bradley, J. M., Pathangey, L. B., Madsen, C. S., Cohen, P. A., Gendler, S. J., and Boons, G. J. (2011) Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine, Proc. Natl. Acad. Sci. USA, 109, 261–266; doi: 10.1073/pnas.1115166109.CrossRefGoogle Scholar
  32. 32.
    Westerlind, U., and Kunz, H. (2011) Synthetic vaccines from tumor-associated glycopeptide antigens, Chimia (Aarau), 65, 30–34; doi: 10.2533/chimia.2011.30.CrossRefGoogle Scholar
  33. 33.
    Turner, M. S., Cohen, P. A., and Finn, O. J. (2007) Lack of effective MUC1 tumor antigen-specific immunity in MUC1-transgenic mice results from a Th/T regulatory cell imbalance that can be corrected by adoptive transfer of wild-type Th cells, J. Immunol., 178, 2787–2793; doi: 10.4049/jimmunol.178.5.2787.CrossRefGoogle Scholar
  34. 34.
    Thatte, J., Qadri, A., Radu, C., and Ward, E. S. (1999) Molecular requirements for T cell recognition by a major histocompatibility complex class II-restricted T cell receptor: the involvement of the fourth hypervariable loop of the Vα domain, J. Exp. Med., 189, 509–520; doi: 10.1084/jem. 189.3.509.CrossRefGoogle Scholar
  35. 35.
    Heath, W. R., and Carbone, F. R. (2001) Cross-presentation, dendritic cells, tolerance and immunity, Annu. Rev. Immunol., 19, 47–64, doi: 10.1146/annurev.immunol.19.1. 47.CrossRefGoogle Scholar
  36. 36.
    Belz, G., Smith, C., Bharadwaj, M., Rice, A., and Jackson, D. (2004) DCs as targets for vaccine design, Cytotherapy, 6, 88–98; doi: 10.1080/14653240410005276.CrossRefGoogle Scholar
  37. 37.
    Oizumi, S., Strbo, N., Pahwa, S., Deyev, V., and Podack, E. R. (2007) Molecular and cellular requirements for enhanced antigen cross-presentation to CD8 cytotoxic T lymphocytes, J. Immunol., 179, 2310–2317; doi: 10.4049/jimmunol.179.4.2310.CrossRefGoogle Scholar
  38. 38.
    Stagg, J., Johnstone, R. W., and Smyth, M. J. (2007) From cancer immunosurveillance to cancer immunotherapy, Immunol. Rev., 220, 82–101; doi: 10.1111/j.1600-065X. 2007.00566.x.CrossRefGoogle Scholar
  39. 39.
    Gad, M., Jensen, T., Gagne, R., Komba, S., Daugaard, S., Kroman, N., Meldal, M., and Werdelin, O. (2003) MUC1-derived glycopeptide libraries with improved MHC anchors are strong antigens and prime mouse T cells for proliferative responses to lysates of human breast cancer tissue, Eur. J. Immunol., 33, 1624–1632; doi: 10.1002/eji.200323698.CrossRefGoogle Scholar
  40. 40.
    Rughetti, A., Biffoni, M., Sabbatucci, M., Rahimi, H., Pellicciotta, I., Fattorossi, A., Pierelli, L., Scambia, G., Lavitrano, M., Frati, L., and Nuti, M. (2000) Transfected human dendritic cells to induce antitumor immunity, Gene Ther., 7, 1458–1466; doi: 10.1038/sj.gt.3301266.CrossRefGoogle Scholar
  41. 41.
    Pecher, G., Spahn, G., Schirrmann, T., Kulbe, H., Ziegner, M., Schenk, J. A., and Sandig, V. (2001) Mucin gene (MUC1) transfer into human dendritic cells by cation-ic liposomes and recombinant adenovirus, Anticancer Res., 21, 2591–2596.Google Scholar
  42. 42.
    North, S., and Butts, C. (2005) Vaccination with BLP25 liposome vaccine to treat non-small cell lung and prostate cancers, Expert Rev. Vaccines, 4, 249–257; doi: 10.1586/14760584.4.3.249.CrossRefGoogle Scholar
  43. 43.
    Wilkie, S., Picco, G., Foster, J., Davies, D. M., Julien, S., Cooper, L., Arif, S., Mather, S. J., Taylor-Papadimitriou, J., Burchell, J. M., and Maher, J. (2008) Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor, J. Immunol., 180, 4901–4909; doi: 10.4049/jimmunol.180.7.4901.CrossRefGoogle Scholar
  44. 44.
    Roulois, D., Gregoire, M., and Fonteneau, J. F. (2013) MUC1-specific cytotoxic T lymphocytes in cancer therapy: induction and challenge, Biomed. Res. Int., 2013, 871936; doi: 10.1155/2013/871936.Google Scholar
  45. 45.
    Apostolopoulos, V., Pietersz, G. A., Tsibanis, A., Tsikkinis, A., Drakaki, H., Loveland, B. E., Piddlesden, S. J., Plebanski, M., Pouniotis, D. S., Alexis, M. N., McKenzie, I. F., and Vassilaros, S. (2006) Pilot phase III immunother-apy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835], Breast Cancer Res., 8, R27; doi: 10.1186/bcr1505.Google Scholar
  46. 46.
    Wright, S. E., Rewers-Felkins, K. A., Quinlin, I. S., Phillips, C. A., Townsend, M., Philip, R., Zorsky, P., Klug, P., Dai, L., Hussain, M., Thomas, A. A., and Sundaramurthy, C. (2009) Tumor burden influences cyto-toxic T cell development in metastatic breast cancer patients - a phase I/II study, Immun. Invest., 38, 820–838; doi: 10.3109/08820130903278089.CrossRefGoogle Scholar
  47. 47.
    Mohebtash, M., Tsang, K. Y., Madan, R. A., Huen, N. Y., Poole, D. J., Jochems, C., Jones, J., Ferrara, T., Heery, C. R., Arlen, P. M., Steinberg, S. M., Pazdur, M., Rauckhorst, M., Jones, E. C., Dahut, W. L., Schlom, J., and Gulley, J. L. (2011) A pilot study of MUC-1/CEA/TRICOM poxvi-ral-based vaccine in patients with metastatic breast and ovarian cancer, Clin. Cancer Res., 17, 7164–7173; doi: 10.1158/1078-0432.CCR-11-0649.CrossRefGoogle Scholar
  48. 48.
    Pegram, M. D., Borges, V. F., Ibrahim, N., Fuloria, J., Shapiro, C., Perez, S., Wang, K., Stark, S. F., and Luck, C. N. (2009) Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer, Breast Cancer Res., 11, R73; doi: 10.1186/bcr2409.Google Scholar
  49. 49.
    Ramlau, R., Quoix, E., Rolski, J., Pless, M., Lena, H., Levy, E., Krzakowski, M., Hess, D., Tartour, E., Chenard, M. P., Limacher, J. M., Bizouarne, N., Acres, B., Halluard, C., and Velu, T. (2008) A phase II study of Tg4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage III/IV non-small cell lung cancer, J. Thorac. Oncol., 3, 735–744; doi: 10.1097/JTO.0b013e31817c6b4f.CrossRefGoogle Scholar
  50. 50.
    Quoix, E., Ramlau, R., Westeel, V., Papai, Z., Madroszyk, A., Riviere, A., Koralewski, P., Breton, J. L, Stoelben, E., Braun, D., Debieuvre, D., Lena, H., Buyse, M., Chenard, M. P., Acres, B., Lacoste, G., Bastien, B., Tavernaro, A., Bizouarne, N., Bonnefoy, J. Y., and Limacher, J. M. (2011) Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial, Lancet Oncol., 12, 1125–1133; doi: 10.1016/S1470-2045(11)70259-5.CrossRefGoogle Scholar
  51. 51.
    Ohyanagi, F., Horai, T., Sekine, I., Yamamoto, N., Nakagawa, K., Nishio, M., Senger, S., Morsli, N., and Tamura, T. (2011) Safety of BLP25 liposome vaccine (L-BLP25) in Japanese patients with unresectable stage III NSCLC after primary chemoradiotherapy: preliminary results from a phase I/II study, Jpn. J. Clin. Oncol., 41, 718–722; doi: 10.1093/jjco/hyr021.CrossRefGoogle Scholar
  52. 52.
    Butts, C., Maksymiuk, A., Goss, G., Soulieres, D., Marshall, E., Cormier, Y., Ellis, P. M., Price, A., Sawhney, R., Beier, F., Falk, M., and Murray, N. (2011) Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial, J. Cancer Res. Clin. Oncol., 137, 1337–1342; doi: 10.1007/s00432-011-1003-3.CrossRefGoogle Scholar
  53. 53.
    Wu, Y. L., Park, K., Soo, R. A., Sun, Y., Tyroller, K., Wages, D., Ely, G., Yang, J. C. H., and Mok, T. (2011) INSPIRE: a phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer, BMC Cancer, 11, 430; doi: 10.1186/1471-2407-11-430.Google Scholar
  54. 54.
    Butts, C., Murray, R. N., Smith, C. J., Ellis, P. M., Jasas, K., Maksymiuk, A., Goss, G., Ely, G., Beier, F., and Soulieres, D. (2010) A multicenter open-label study to assess the safety of a new formulation of BLP25 liposome vaccine in patients with unresectable stage III non-small-cell lung cancer, Clin. Lung Cancer, 11, 391–395; doi: 10.3816/CLC.2010.n.101.CrossRefGoogle Scholar
  55. 55.
    Lepisto, A. J., Moser, A. J., Zeh, H., Lee, K., Bartlett, D., McKolanis, J. R., Geller, B. A., Schmotzer, A., Potter, D. P., Whiteside, T., Finn, O. J., and Ramanathan, R. K. (2008) A phase I/II study of a MUC1 peptide pulsed autol-ogous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors, Cancer Ther., 6, 955–964.Google Scholar
  56. 56.
    Kondo, H., Hazama, S., Kawaoka, T., Yoshino, S., Yoshida, S., Tokuno, K., Takashima, M., Ueno, T., Hinoda, Y., and Oka, M. (2008) Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes, Anticancer Res., 28, 379–387.Google Scholar
  57. 57.
    Dreicer, R., Stadler, W. M., Ahmann, F. R., Whiteside, T., Bizouarne, N., Acres, B., Limacher, J. M., Squiban, P., and Pantuck, A. (2009) MVA-MUC1-IL2 vaccine immunotherapy (TG4010) improves PSA doubling time in patients with prostate cancer with biochemical failure, Invest. New Drugs, 27, 379–386; doi: 10.1007/s10637-008-9187-3.CrossRefGoogle Scholar
  58. 58.
    Dobrzanski, M. J., Rewers-Felkins, K. A., Samad, K. A., Quinlin, I. S., Phillips, C. A., Robinson, W., Dobrzanski, D. J., and Wright, S. E. (2012) Immunotherapy with IL-10- and IFN-γ-producing CD4 effector cells modulate “Natural” and “Inducible” CD4 TReg cell subpopulation levels: observations in four cases of patients with ovarian cancer, Cancer Immunol. Immunother., 61, 839–854; doi: 10.1007/s00262-011-1128-x.CrossRefGoogle Scholar
  59. 59.
    Rittig, S. M., Haentschel, M., Weimer, K. J., Heine, A., Muller, M. R., Brugger, W., Horger, M. S., Maksimovic, O., Stenzl, A., Hoerr, I., Rammensee, H. G., Holderried, T. A., Kanz, L., Pascolo, S., and Brossart, P. (2011) Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients, Mol. Ther., 19, 990–999; doi: 10.1038/mt.2010.289.CrossRefGoogle Scholar
  60. 60.
    Oudard, S., Rixe, O., Beuselinck, B., Linassier, C., Banu, E., Machiels, J. P., Baudard, M., Ringeisen, F., Velu, T., Lefrere-Belda, M. A., Limacher, J. M., Fridman, W. H., Azizi, M., Acres, B., and Tartour, E. (2011) A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal clear-cell carcinoma: clinical and immunological findings, Cancer Immunol. Immunother., 60, 261–271; doi: 10.1007/s00262-010-0935-9.CrossRefGoogle Scholar
  61. 61.
    Syrkina, M. S., Vassetzky, Y. S., and Rubtsov, M. A. (2019) MUC1 story: great expectations, disappointments and the renaissance, Curr. Med. Chem., 26, 1–10; doi: 10.2174/0929867324666170817151954.CrossRefGoogle Scholar
  62. 62.
    Taylor-Papadimitriou, J., Burchell, J. M., Graham, R., and Beatson, R. (2018) Latest developments in MUC1 immunotherapy, Biochem. Soc. Trans., 46, 659–668; doi: 10.1042/BST20170400.CrossRefGoogle Scholar
  63. 63.
    Zhang, L., Vlad, A., Milcarek, C., and Finn, O. J. (2013) Human mucin MUC1 RNA undergoes different types of alternative splicing resulting in multiple isoforms, Cancer Immunol. Immunother., 62, 423–435; doi: 10.1007/s00262-012-1325-2.CrossRefGoogle Scholar
  64. 64.
    Zrihan-Licht, S., Vos, H. L., Baruch, A., Elroy-Stein, O., Sagiv, D., Keydar, I., Hilkens, J., and Wreschner, D. H. (1994) Characterization and molecular cloning of a novel MUC1 protein, devoid of tandem repeats, expressed in human breast cancer tissue, Eur. J. Biochem., 224, 787–795.CrossRefGoogle Scholar
  65. 65.
    Oosterkamp, H. M., Scheiner, L., Stefanova, M. C., Lloyd, K. O., and Finstad, C. L. (1997) Comparison of MUC-1 mucin expression in epithelial and non-epithelial cancer cell lines and demonstration of a new short variant form (MUC-1/Z), Int. J. Cancer, 72, 87–94.CrossRefGoogle Scholar
  66. 66.
    Hanisch, F. G., and Muller, S. (2000) MUC1: the polymorphic appearance of a human mucin, Glycobiology, 10, 439–449.CrossRefGoogle Scholar
  67. 67.
    Schut, I. C., Waterfall, P. M., Ross, M., O’Sullivan, C., Miller, W. R., Habib, F. K., and Bayne, C. W. (2003) MUC1 expression, splice variant and short form transcription (MUC1/Z, MUC1/Y) in prostate cell lines and tissue, BJU Int., 91, 278–283; doi: 10.1046/j.1464-410X.2003.03062.x.CrossRefGoogle Scholar
  68. 68.
    Baruch, A., Hartmann, M., Zrihan-Licht, S., Greenstein, S., Burstein, M., Keydar, I., Weiss, M., Smorodinsky, N., and Wreschner, D. H. (1997) Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function, Int. J. Cancer, 71, 741–749; doi: 10.1002/(SICI)1097-0215(19970529)71:53.0. CO;2-R.CrossRefGoogle Scholar
  69. 69.
    Horinouchi, M., Nagata, K., Nakamura, A., Goto, M., Takao, S., Sakamoto, M., Fukushima, N., Miwa, A., Irimura, T., Imai, K., Sato, E., and Yonezawa, S. (2003) Expression of different glycoforms of membrane mucin (MUC1) and secretory mucin (MUC2, MUC5AC and MUC6) in pancreatic neoplasms, Acta Histochem. Cytochem., 36, 443–453; doi: 10.1267/ahc.36.443.CrossRefGoogle Scholar
  70. 70.
    Higashi, M., Yonezawa, S., Ho, J. J., Tanaka, S., Irimura, T., Kim, Y. S., and Sato, E. (1999) Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: its relationship with a new morphological classification of cholangiocarcinoma, Hepatology, 30, 1347–1355; doi: 10.1002/hep.510300609.CrossRefGoogle Scholar
  71. 71.
    Tamada, S., Goto, M., Nomoto, M., Nagata, K., Shimizu, T., Tanaka, S., Sakoda, K., Imai, K., and Yonezawa, S. (2002) Expression of MUC1 and MUC2 mucins in extra-hepatic bile duct carcinomas: its relationship with tumor progression and prognosis, Pathol. Int., 52, 713–723; doi: 10.1046/j.1440-1827.2002.01414.x.CrossRefGoogle Scholar
  72. 72.
    Utsunomiya, T., Yonezawa, S., Sakamoto, H., Kitamura, H., Hokita, S., Aiko, T., Tanaka, S., Irimura, T., Kim, Y. S., and Sato, E. (1998) Expression of MUC1 and MUC2 mucins in gastric carcinomas: its relationship with the prognosis of the patients, Clin. Cancer Res., 4, 2605–2614.Google Scholar
  73. 73.
    Matsukita, S., Nomoto, M., Kitajima, S., Tanaka, S., Goto, M., Irimura, T., Kim, Y. S., Sato, E., and Yonezawa, S. (2003) Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast: comparison with invasive ductal carcinoma, Histopathology, 42, 26–36; doi: 10.1046/j.1365-2559. 2003.01530.x.CrossRefGoogle Scholar
  74. 74.
    Muller, S., Alving, K., Peter-Katalinic, J., Zachara, N., Gooley, A. A., and Hanisch, F. G. (1999) High density O-glycosylation on tandem repeat peptide from secretory MUC1 of T47D breast cancer cells, J. Biol. Chem., 274, 18165–18172; doi: 10.1074/jbc.274.26.18165.CrossRefGoogle Scholar
  75. 75.
    Nakamori, S., Ota, D. M., Cleary, K. R., Shirotani, K., and Irimura, T. (1994) MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma, Gastroenterology, 106, 353–361; doi: 10.1016/0016-5085(94)90592-4.CrossRefGoogle Scholar
  76. 76.
    Levitin, F., Stern, O., Weiss, M., Gil-Henn, C., Ziv, R., Prokocimer, Z., Smorodinsky, N. I., Rubinstein, D. B., and Wreschner, D. H. (2005) The MUC1 SEA module is a self-cleaving domain, J. Biol. Chem., 280, 33374–33386; doi: 10.1074/jbc.M506047200.CrossRefGoogle Scholar
  77. 77.
    Thathiah, A., Blobel, C. P., and Carson, D. D. (2003) Tumor necrosis factor-α converting enzyme/ADAM 17 mediates MUC1 shedding, J. Biol. Chem., 278, 3386–3394; doi: 10.1074/jbc.M208326200.CrossRefGoogle Scholar
  78. 78.
    Thathiah, A., and Carson, D. D. (2004) MT1-MMP mediates MUC1 shedding independent of TACE/ADAM17, Biochem. J., 382, 363–373; doi: 10.1042/BJ20040513.CrossRefGoogle Scholar
  79. 79.
    Carson, D. D. (2008) The cytoplasmic tail of MUC1: a very busy place, Sci. Signal., 1, pe35; doi: 10.1126/scisig-nal.127pe35.Google Scholar
  80. 80.
    Kovjazin, R., Volovitz, I., Kundel, Y., Rosenbaum, E., Medalia, G., Horn, G., Smorodinsky, N. I., Brenner, B., and Carmon, L. (2011) ImMucin: a novel therapeutic vaccine with promiscuous MHC binding for the treatment of MUC1-expressing tumors, Vaccine, 29, 4676–4686; doi: 10.1016/j.vaccine.2011.04.103.CrossRefGoogle Scholar
  81. 81.
    Uchida, Y., Raina, D., Kharbanda, S., and Kufe, D. (2013) Inhibition of the MUC1-C oncoprotein is synergistic with cytotoxic agents in the treatment of breast cancer cells, Cancer Biol. Ther., 14, 127–134; doi: 10.4161/cbt.22634.CrossRefGoogle Scholar
  82. 82.
    Wu, A. A., Drake, V., Huang, H. S., Chiu, S. C., and Zheng, L. (2015) Reprogramming the tumor microenvi-ronment: tumor-induced immunosuppressive factors paralyze T cells, Oncoimmunology, 4, e1016700; doi: 10.1080/2162402X.2015.1016700.Google Scholar
  83. 83.
    Rabinovich, G. A., Gabrilovich, D., and Sotomayor, E. M. (2007) Immunosuppressive strategies that are mediated by tumor cells, Annu. Rev. Immunol., 25, 267–296; doi: 10.1146/annurev.immunol.25.022106.141609.CrossRefGoogle Scholar
  84. 84.
    Vasilevko, V., Ghochikyan, A., Sadzikava, N., Petrushina, I., Tran, M., Cohen, E. P., Kesslak, P. J., Cribbs, D. H., Nicolson, G. L., and Agadjanyan, M. G. (2003) Immunization with a vaccine that combines the expression of MUC1 and B7 co-stimulatory molecules prolongs the survival of mice and delays the appearance of mouse mammary tumors, Clin. Exp. Metastasis, 20, 489–498; doi: 10.1023/A:1025802610724.CrossRefGoogle Scholar
  85. 85.
    Liu, L., Wang, Y., Miao, L., Liu, Q., Musetti, S., Li, J., and Huan, L. (2018) Combination immunotherapy of MUC1 mRNA nano-vaccine and CTLA-4 blockade effectively inhibits growth of triple negative breast cancer, Mol. Ther., 26, 45–55; doi: 10.1016/j.ymthe.2017.10.020.CrossRefGoogle Scholar
  86. 86.
    Marvel, D. M., and Finn, O. J. (2014) Global inhibition of DC priming capacity in the spleen of self-antigen vaccinated mice requires IL-10, Front. Immunol., 5, 59; doi: 10.3389/fimmu.2014.00059.Google Scholar
  87. 87.
    Agrawal, B., and Longenecker, B. M. (2005) MUC1 mucin-mediated regulation of human T cells, Int. Immunol., 17, 391–399; doi: 10.1093/intimm/dxh219.CrossRefGoogle Scholar
  88. 88.
    Agrawal, B., Krantz, M. J., Parker, J., and Longenecker, B. M. (1998) Expression of MUC1 mucin on activated human T-cells: implications for a role of MUC1 in normal immune regulation, Cancer Res., 58, 4079–4081.Google Scholar
  89. 89.
    Gendler, S. J. (2001) MUC1, the renaissance molecule, J. Mammary Gland. Biol. Neoplasia, 6, 339–353.CrossRefGoogle Scholar
  90. 90.
    Correa, I., Plunkett, T., Vlad, A., Mungul, A., Candelora-Kettel, J., Burchell, J. M., Taylor-Papadimitriou, J., and Finn, O. J. (2003) Form and pattern of MUC1 expression on T cells activated in vivo or in vitro suggests a function in T-cell migration, Immunology, 108, 32–41; doi: 10.1046/j.1365-2567.2003.01562.x.CrossRefGoogle Scholar
  91. 91.
    Tsang, J. Y. S., Chai, J. G., and Lechler, R. (2003) Antigen presentation by mouse CD4+ T cells involving acquired MHC class II: peptide complexes: another mechanism to limit clonal expansion? Blood, 101, 2704–2710; doi: 10.1182/blood-2002-04-1230.CrossRefGoogle Scholar
  92. 92.
    Agrawal, B., Gupta, N., and Konowalchuk, J. D. (2018) MUC1 mucin: a putative regulatory (checkpoint) molecule of T cells, Front. Immunol., 9, 2391; doi: 10.3389/fimmu. 2018.02391.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  1. 1.Department of BiologyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Laboratoire Franco-Russe de Recherches en OncologieLomonosov Moscow State UniversityMoscowRussia
  3. 3.Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia

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