Generation of a novel long-acting thymosin alpha1-Fc fusion protein and its efficacy for the inhibition of breast cancer in vivo

Biomedicine and Pharmacotherapy

Volumn 108, Issue , 2018, Pages 610-617

  Shen, Xutong ^a   Li, Qingqing ^a   Wang, Fanwen ^a   Bao, Jingxiao ^a   Dai, Mengting ^a   Zheng, Heng ^a   Lao, Xingzhen ^a  

^a CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Antitumor; Cancer immunotherapy; Immunoregulation; Long acting fusion protein

Indexed keywords

BACTERIUM LYSATE; FC FUSION PROTEIN; FUSION PROTEIN; GAMMA INTERFERON; IMMUNOGLOBULIN G1; INTERLEUKIN 2; PACLITAXEL; THYMOSIN ALPHA1; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; IMMUNOGLOBULIN FC FRAGMENT; IMMUNOGLOBULIN G;

4T1 CELL LINE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER GROWTH; CANCER INHIBITION; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; FEMALE; IMMUNOSUPPRESSIVE TREATMENT; IN VIVO STUDY; LYMPHOCYTIC INFILTRATION; MCF-7 CELL LINE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN PURIFICATION; RAT; SINGLE DRUG DOSE; THYMUS ATROPHY; TUMOR MODEL; TUMOR REGRESSION; TUMOR WEIGHT; WESTERN BLOTTING; ANIMAL; BAGG ALBINO MOUSE; BREAST TUMOR; DRUG EFFECT; HUMAN; INSTITUTE FOR CANCER RESEARCH MOUSE; METABOLISM; NUDE MOUSE; TUMOR CELL LINE; WISTAR RAT;

ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE, TUMOR; FEMALE; HUMANS; IMMUNOGLOBULIN FC FRAGMENTS; IMMUNOGLOBULIN G; INTERFERON-GAMMA; INTERLEUKIN-2; MCF-7 CELLS; MICE; MICE, INBRED BALB C; MICE, INBRED ICR; MICE, NUDE; RATS; RATS, WISTAR; THYMALFASIN;

EID: 85053452318     PISSN: 07533322     EISSN: 19506007     Source Type: Journal    
DOI: 10.1016/j.biopha.2018.09.064     Document Type: Article

References (57)

1. Nicolini, A., Ferrari, P., Diodati, L., Carpi, A., Recent advances in comprehending the signaling pathways involved in the progression of breast Cancer. Int. J. Mol. Sci., 18(11), 2017.
2. Venkatesan, J., Anil, S., Kim, S.K., Shim, M.S., Marine fish proteins and peptides for cosmeceuticals: a review. Mar. Drugs, 15(5), 2017.
3. Oudart, J.B., Brassart-Pasco, S., Vautrin, A., Sellier, C., Machado, C., Dupont-Deshorgue, A., Brassart, B., Baud, S., Dauchez, M., Monboisse, J.C., Harakat, D., Maquart, F.X., Ramont, L., Plasmin releases the anti-tumor peptide from the NC1 domain of collagen XIX. Oncotarget 6:6 (2015), 3656–3668.
4. Yang, H., Feng, Y., Cai, H., Jia, D., Li, H., Tao, Z., Zhong, Y., Li, Z., Shi, Q., Wan, L., Li, L., Lu, X., Endogenous IgG-based affinity-controlled release of TRAIL exerts superior antitumor effects. Theranostics 8:9 (2018), 2459–2476.
5. Goldstein, A.L., Low, T.L., McAdoo, M., McClure, J., Thurman, G.B., Rossio, J., Lai, C.Y., Chang, D., Wang, S.S., Harvey, C., Ramel, A.H., Meienhofer, J., Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc. Natl. Acad. Sci. U. S. A. 74:2 (1977), 725–729.
6. Lunin, S.M., Glushkova, O.V., Khrenov, M.O., Novoselova, T.V., Parfenyuk, S.B., Fesenko, E.E., Novoselova, E.G., Thymic peptides restrain the inflammatory response in mice with experimental autoimmune encephalomyelitis. Immunobiology 218:3 (2013), 402–407.
7. Romani, L., Bistoni, F., Montagnoli, C., Gaziano, R., Bozza, S., Bonifazi, P., Zelante, T., Moretti, S., Rasi, G., Garaci, E., Puccetti, P., Thymosin alpha1: an endogenous regulator of inflammation, immunity, and tolerance. Ann. N. Y. Acad. Sci. 1112 (2007), 326–338.
8. Romani, L., Oikonomou, V., Moretti, S., Iannitti, R.G., D'Adamo, M.C., Villella, V.R., Pariano, M., Sforna, L., Borghi, M., Bellet, M.M., Fallarino, F., Pallotta, M.T., Servillo, G., Ferrari, E., Puccetti, P., Kroemer, G., Pessia, M., Maiuri, L., Goldstein, A.L., Garaci, E., Thymosin alpha1 represents a potential potent single-molecule-based therapy for cystic fibrosis. Nat. Med. 23:5 (2017), 590–600.
9. Garaci, E., Pica, F., Serafino, A., Balestrieri, E., Matteucci, C., Moroni, G., Sorrentino, R., Zonfrillo, M., Pierimarchi, P., Sinibaldi-Vallebona, P., Thymosin alpha1 and cancer: action on immune effector and tumor target cells. Ann. N. Y. Acad. Sci. 1269 (2012), 26–33.
10. Danielli, R., Fonsatti, E., Calabro, L., Di Giacomo, A.M., Maio, M., Thymosin alpha1 in melanoma: from the clinical trial setting to the daily practice and beyond. Ann. N. Y. Acad. Sci. 1270 (2012), 8–12.
11. King, R.S., Tuthill, C., Evaluation of thymosin alpha 1 in nonclinical models of the immune-suppressing indications melanoma and sepsis. Expert Opin. Biol. Ther. 15 (2015), S41–S49.
12. Maio, M., Mackiewicz, A., Testori, A., Trefzer, U., Ferraresi, V., Jassem, J., Garbe, C., Lesimple, T., Guillot, B., Gascon, P., Gilde, K., Camerini, R., Cognetti, F., Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. J. Clin. Oncol. 28:10 (2010), 1780–1787.
13. Moody, T.W., Fagarasan, M., Zia, F., Cesnjaj, M., Goldstein, A.L., Thymosin alpha 1 down-regulates the growth of human non-small cell lung cancer cells in vitro and in vivo. Cancer Res. 53:21 (1993), 5214–5218.
14. Moody, T.W., Tuthill, C., Badamchian, M., Goldstein, A.L., Thymosin alpha(1) inhibits mammary carcinogenesis in Fisher rats. Peptides 23:5 (2002), 1011–1014.
15. Li, C.C., Bo, L.Y., Liu, Q.Q., Jin, F.G., Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysis. Int. J. Infect. Dis. 33 (2015), 90–96.
16. Xiang, X.S., Li, N., Zhao, Y.Z., Li, Q.R., Li, J.S., Combination therapy with thymosin alpha1 and dexamethasone helps mice survive sepsis. Inflammation 37:2 (2014), 402–416.
17. Wu, J., Zhou, L., Liu, J., Ma, G., Kou, Q., He, Z., Chen, J., Ou-Yang, B., Chen, M., Li, Y., Wu, X., Gu, B., Chen, L., Zou, Z., Qiang, X., Chen, Y., Lin, A., Zhang, G., Guan, X., The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit. Care, 17(1), 2013, R8.
18. You, J., Zhuang, L., Cheng, H.Y., Yan, S.M., Yu, L., Huang, J.H., Tang, B.Z., Huang, M.L., Ma, Y.L., Chongsuvivatwong, V., Sriplung, H., Geater, A., Qiao, Y.W., Wu, R.X., Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: a randomized controlled study. World J. Gastroenterol. 12:41 (2006), 6715–6721.
19. Yang, Y.F., Zhao, W., Zhong, Y.D., Yang, Y.J., Shen, L., Zhang, N., Huang, P., Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysis. Antiviral Res. 77:2 (2008), 136–141.
20. Chien, R.N., Liaw, Y.F., Chen, T.C., Yeh, C.T., Sheen, I.S., Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology 27:5 (1998), 1383–1387.
21. Vaishya, R., Khurana, V., Patel, S., Mitra, A.K., Long-term delivery of protein therapeutics. Expert Opin. Drug Deliv. 12:3 (2015), 415–440.
22. Ceaglio, N., Etcheverrigaray, M., Kratje, R., Oggero, M., Influence of carbohydrates on the stability and structure of a hyperglycosylated human interferon alpha mutein. Biochimie 92:8 (2010), 971–978.
23. Ciepluch, K., Radulescu, A., Hoffmann, I., Raba, A., Allgaier, J., Richter, D., Biehl, R., Influence of PEGylation on Domain Dynamics of Phosphoglycerate Kinase: PEG Acts Like Entropic Spring for the Protein. Bioconjugate Chem. 29:6 (2018), 1950–1960.
24. Sioud, M., Westby, P., Olsen, J.K.E., Mobergslien, A., Generation of new peptide-Fc fusion proteins that mediate antibody-dependent cellular cytotoxicity against different types of cancer cells. Mol. Ther. Methods Clin. Dev., 2, 2015.
25. Tracey, D., Klareskog, L., Sasso, E.H., Salfeld, J.G., Tak, P.P., Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol. Ther. 117:2 (2008), 244–279.
26. Umpierrez, G.E., Blevins, T., Rosenstock, J., Cheng, C., Anderson, J.H., Bastyr, E.J. 3rd, E.G.O.S. Group, The effects of LY2189265, a long-acting glucagon-like peptide-1 analogue, in a randomized, placebo-controlled, double-blind study of overweight/obese patients with type 2 diabetes: the EGO study. Diabetes Obes. Metab. 13:5 (2011), 418–425.
27. Klareskog, L., van der Heijde, D., de Jager, J.P., Gough, A., Kalden, J., Malaise, M., Mola, E.M., Pavelka, K., Sany, J., Settas, L., Wajdula, J., Pedersen, R., Fatenejad, S., Sanda, M., Investigators, T.S., Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363:9410 (2004), 675–681.
28. Molineux, G., Newland, A., Development of romiplostim for the treatment of patients with chronic immune thrombocytopenia: from bench to bedside. Br. J. Haematol. 150:1 (2010), 9–20.
29. Sockolosky, J.T., Szoka, F.C., The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy. Adv. Drug Deliv. Rev. 91 (2015), 109–124.
30. Rath, T., Baker, K., Dumont, J.A., Peters, R.T., Jiang, H.Y., Qiao, S.W., Lencer, W.I., Pierce, G.F., Blumberg, R.S., Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit. Rev. Biotechnol. 35:2 (2015), 235–254.
31. Deissler, H.L., Lang, G.K., Lang, G.E., Neonatal Fc receptor FcRn is involved in intracellular transport of the Fc fusion protein aflibercept and its transition through retinal endothelial cells. Exp. Eye Res. 154 (2017), 39–46.
32. Kellner, C., Derer, S., Valerius, T., Peipp, M., Boosting ADCC and CDC activity by Fc engineering and evaluation of antibody effector functions. Methods 65:1 (2014), 105–113.
33. Wu, B., Sun, Y.N., Pharmacokinetics of Peptide-Fc fusion proteins. J. Pharm. Sci. 103:1 (2014), 53–64.
34. Shimamoto, G., Gegg, C., Boone, T., Queva, C., Peptibodies: a flexible alternative format to antibodies. MAbs 4:5 (2012), 586–591.
35. Huang, C., Receptor-Fc fusion therapeutics, traps, and MIMETIBODY technology. Curr. Opin. Biotechnol. 20:6 (2009), 692–699.
36. Carlson, K.R., Pomerantz, S.C., Li, J., Vafa, O., Naso, M., Strohl, W., Mains, R.E., Eipper, B.A., Secretion of Fc-amidated peptide fusion proteins by Chinese hamster ovary cells. BMC Biotechnol., 15, 2015, 61.
37. Kammertoens, T., Friese, C., Arina, A., Idel, C., Briesemeister, D., Rothe, M., Ivanov, A., Szymborska, A., Patone, G., Kunz, S., Sommermeyer, D., Engels, B., Leisegang, M., Textor, A., Fehling, H.J., Fruttiger, M., Lohoff, M., Herrmann, A., Yu, H., Weichselbaum, R., Uckert, W., Hubner, N., Gerhardt, H., Beule, D., Schreiber, H., Blankenstein, T., Tumour ischaemia by interferon-gamma resembles physiological blood vessel regression. Nature 545:7652 (2017), 98–102.
38. Matsuzaki, J., Tsuji, T., Luescher, I.F., Shiku, H., Mineno, J., Okamoto, S., Old, L.J., Shrikant, P., Gnjatic, S., Odunsi, K., Direct tumor recognition by a human CD4(+) T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses. Sci. Rep. Uk, 5, 2015.
39. Ndhlovu, L.C., Leal, F.E., Eccles-James, I.G., Jha, A.R., Lanteri, M., Norris, P.J., Barbour, J.D., Wachter, D.J., Andersson, J., Tasken, K., Torheim, E.A., Aandahl, E.M., Kallas, E.G., Nixon, D.F., A novel human CD4+ T-cell inducer subset with potent immunostimulatory properties. Eur. J. Immunol. 40:1 (2010), 134–141.
40. Goldstein, A.L., Goldstein, A.L., From lab to bedside: emerging clinical applications of thymosin alpha 1. Expert Opin. Biol. Ther. 9:5 (2009), 593–608.
41. Broudy, V.C., Lin, N.L., AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine 25:2 (2004), 52–60.
42. Gao, G.F., Jakobsen, B.K., Molecular interactions of coreceptor CD8 and MHC class I: the molecular basis for functional coordination with the T-cell receptor. Immunol. Today 21:12 (2000), 630–636.
43. Purbhoo, M.A., Boulter, J.M., Price, D.A., Vuidepot, A.L., Hourigan, C.S., Dunbar, P.R., Olson, K., Dawson, S.J., Phillips, R.E., Jakobsen, B.K., Bell, J.I., Sewell, A.K., The human CD8 coreceptor effects cytotoxic T cell activation and antigen sensitivity primarily by mediating complete phosphorylation of the T cell receptor zeta chain. J. Biol. Chem. 276:35 (2001), 32786–32792.
44. Sewell, A.K., Gerth, U.C., Price, D.A., Purbhoo, M.A., Boulter, J.M., Gao, G.F., Bell, J.I., Phillips, R.E., Jakobsen, B.K., Antagonism of cytotoxic T-lymphocyte activation by soluble CD8. Nat. Med. 5:4 (1999), 399–404.
45. Nilofar Danishmalik, S., Lee, S.H., Sin, J.I., Tumor regression is mediated via the induction of HER263-71- specific CD8+ CTL activity in a 4T1.2/HER2 tumor model: no involvement of CD80 in tumor control. Oncotarget 8:16 (2017), 26771–26788.
46. Shen, L., Krauthauser, S., Fischer, K., Hobernik, D., Abassi, Y., Dzionek, A., Nikolaev, A., Voltz, N., Diken, M., Krummen, M., Montermann, E., Tubbe, I., Lorenz, S., Strand, D., Schild, H., Grabbe, S., Bros, M., Vaccination with trifunctional nanoparticles that address CD8+ dendritic cells inhibits growth of established melanoma. Nanomedicine 11:20 (2016), 2647–2662.
47. Rodriguez-Ruiz, M.E., Rodriguez, I., Garasa, S., Barbes, B., Solorzano, J.L., Perez-Gracia, J.L., Labiano, S., Sanmamed, M.F., Azpilikueta, A., Bolanos, E., Sanchez-Paulete, A.R., Aznar, M.A., Rouzaut, A., Schalper, K.A., Jure-Kunkel, M., Melero, I., Abscopal effects of radiotherapy are enhanced by combined immunostimulatory mAbs and are dependent on CD8 t cells and Crosspriming. Cancer Res. 76:20 (2016), 5994–6005.
48. Matsuzaki, J., Tsuji, T., Luescher, I.F., Shiku, H., Mineno, J., Okamoto, S., Old, L.J., Shrikant, P., Gnjatic, S., Odunsi, K., Direct tumor recognition by a human CD4(+) T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses. Sci. Rep., 5, 2015, 14896.
49. Sohn, H.J., Lee, J.Y., Lee, H.J., Sohn, D.H., Cho, H.I., Kim, H.J., Kim, T.G., Simultaneous in vitro generation of CD8 and CD4 T cells specific to three universal tumor associated antigens of WT1, survivin and TERT and adoptive T cell transfer for the treatment of acute myeloid leukemia. Oncotarget 8:27 (2017), 44059–44072.
50. Williams, M.A., Tyznik, A.J., Bevan, M.J., Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature 441:7095 (2006), 890–893.
51. Feau, S., Arens, R., Togher, S., Schoenberger, S.P., Autocrine IL-2 is required for secondary population expansion of CD8(+) memory T cells. Nat. Immunol. 12:9 (2011), 908–913.
52. Liang, J., Liu, X., Xie, Q., Chen, G., Li, X., Jia, Y., Yin, B., Qu, X., Li, Y., Endostatin enhances antitumor effect of tumor antigen-pulsed dendritic cell therapy in mouse xenograft model of lung carcinoma. Chin. J. Cancer Res. 28:4 (2016), 452–460.
53. Jung, K., Ha, J.H., Kim, J.E., Kim, J.A., Kim, Y.J., Kim, C.H., Kim, Y.S., Heterodimeric Fc-fused IL12 shows potent antitumor activity by generating memory CD8(+) T cells. Oncoimmunology, 7(7), 2018.
54. Kim, Y., Bae, J., Shin, T., Kang, S., Jeong, M., Han, Y., Park, J., Kim, S., Kim, Y., Immunoglobulin Fc-fused, neuropilin-1-specific peptide shows efficient tumor tissue penetration and inhibits tumor growth via anti-angiogenesis. J. Control. Release 216 (2015), 56–68.
55. Mobergslien, A., Peng, Q., Vasovic, V., Sioud, M., Cancer cell-binding peptide fused Fc domain activates immune effector cells and blocks tumor growth. Oncotarget 7:46 (2016), 75940–75953.
56. Pierluigi, B., D'Angelo, C., Fallarino, F., Moretti, S., Zelante, T., Bozza, S., De Luca, A., Bistoni, F., Garaci, E., Romani, L., Thymosin alpha1: the regulator of regulators?. Ann. N. Y. Acad. Sci. 1194 (2010), 1–5.
57. Li, J., Cheng, Y., Zhang, X., Zheng, L., Han, Z., Li, P., Xiao, Y., Zhang, Q., Wang, F., The in vivo immunomodulatory and synergistic anti-tumor activity of thymosin alpha1-thymopentin fusion peptide and its binding to TLR2. Cancer Lett. 337:2 (2013), 237–247.