Immunogenicity Evaluation of Recombinant Edible Vaccine Candidate Containing HER2-MUC1 against Breast Cancer

  • Mahdieh Mehrab Mohseni Department of Agricultural Biotechnology, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
  • Jafar Amani Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
  • Mahdi Fasihi Ramandi Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
  • Forouzandeh Mahjoubi Department of Medical Biotechnology, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
  • Mahyat Jafaria Department of Agricultural Biotechnology, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
  • Ali Hatef Salmanian Department of Agricultural Biotechnology, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
Keywords: Breast cancer, Edible vaccine, HER2, Immunogen, MUC1, Transgenic plant

Abstract

Human epithelial growth factor receptor2 (Her2) and polymorphic epithelial mucin (MUC1) are tumor-associated antigens that have been extensively investigated in adenocarcinomas. Generally, each of these molecules was used separately for diagnosis of adenocarcinomas and as an injective vaccines in cancer therapy researches, but not in the chimeric form as an edible immunogen. In this study, Her2, MUC1, and a novel fusion structure were expressed in the seeds and hairy roots of transgenic plants appropriately. The mice groups were immunized either by feeding of transgenic seeds or hairy roots. All immunized groups showed a considerable rise in anti-glycoprotein serum IgG and IgA, and IFNɣ cytokine. However, the animals received chimeric protein showed significant higher immune responses in comparison to ones received one of these immunogen. The results indicated that the oral immunization of an animal model with transgenic plants could effectively elicit immune responses against two major tumor-associated antigens.

References

1. Reis PC, Dietzmann-Maurer K, Von Scheven E, Burnham J, Sullivan K. SAT0255 Prospective Study: The Role of Urinary HER2 as A Lupus Nephritis Biomarker. Annals of the Rheumatic Diseases 2016; 75:761.
2. English DP, Roque DM, Santin AD. HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies. Mol Diagn Ther 2013; 17(2):85-99.
3. Swain SM, Baselga J, Kim S-B, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372(8):724-34.
4. Taylor-Papadimitriou J, Burchell J, Miles DW, Dalziel M. MUC1 and cancer. Biochim Biophys Acta 1999; 1455(2-3):301-13.
5. Sorensen AL, Reis CA, Tarp MA, Mandel U, Ramachandran K, Sankaranarayanan V, et al. Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance. Glycobiology 2006; 16(2):96-107.
6. Tang CK, Apostolopoulos V. Strategies used for MUC1 immunotherapy: preclinical studies. Expert Rev Vaccines 2008; 7(7):951-62.
7. Tang CK, Katsara M, Apostolopoulos V. Strategies used for MUC1 immunotherapy: human clinical studies. Expert Rev Vaccines 2008; 7(7):963-75.
8. Wong-Arce A, González-Ortega O, Rosales-Mendoza S. Plant-made vaccines in the fight against cancer. Trends Biotechnol 2017; 35(3):241-56.
9. Staub JM, Garcia B, Graves J, Hajdukiewicz PT, Hunter P, Nehra N, et al. High-yield production of a human therapeutic protein in tobacco chloroplasts. Nat Biotechnol 2000; 18(3):333-8.
10. Moustafa K, Makhzoum A, Trémouillaux-Guiller J. Molecular farming on rescue of pharma industry for next generations. Crit Rev Biotechnol 2016; 36(5):840-50.
11. Judge NA, Mason HS, O'Brien AD. Plant cell-based intimin vaccine given orally to mice primed with intimin reduces time of Escherichia coli O157: H7 shedding in feces. Infect Immun 2004; 72(1):168-75.
12. Habibi P, De Sa MFG, Makhzoum A, Malik S, da Silva ALL, Hefferon K, et al. Bioengineering Hairy Roots: Phytoremediation, Secondary Metabolism, Molecular Pharming, Plant-Plant Interactions and Biofuels. Sustainable Agriculture Reviews: Springer 2017:213-51.
13. Lau OS, Sun SS. Plant seeds as bioreactors for recombinant protein production. Biotechnol Adv 2009; 27(6):1015-22.
14. Stöger E, Vaquero C, Torres E, Sack M, Nicholson L, Drossard J, et al. Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies. Plant Mol Biol 2000; 42(4):583-90.
15. Nair B. Plantibodies: Paving Novel Avenues for Immunotherapy. MOJ Surg 2017; 4(4):00078.
16. Barciszewski J, Maciej S, Haertlé T. Minireview: analysis of rape seed napin structure and potential roles of the storage protein. J Protein Chem 2000; 19(4):249-54.
17. Matic S, Quaglino E, Arata L, Riccardo F, Pegoraro M, Vallino M, et al. The rat ErbB2 tyrosine kinase receptor produced in plants is immunogenic in mice and confers protective immunity against ErbB2 mammary cancer. Plant Biotechnol J 2015; 14(1):153-9.
18. Chotprakaikiat W, Allen A, Bui-Minh D, Harden E, Jobsri J, Cavallo F, et al. A plant-expressed conjugate vaccine breaks CD4+ tolerance and induces potent immunity against metastatic Her2+ breast cancer. Oncoimmunology 2016; 5(6):e1166323.
19. Lee JH, Ko K. Production of Recombinant Anti-Cancer Vaccines in Plants. Biomolecules & Therapeutics 2017; 25(4):345-53.
20. Sindarovska Y, Gerasymenko I, Sheludko Y, Olevinskaya Z, Spivak N, Kuchuk N. Production of human interferon ALPHA 2b in plants of Nicotiana excelsior by Agrobacterium-mediated transient expression. Tsitol Genet 2010; 44(5):313-6.
21. Evangelista RL KA, Howard JA, Nikolov ZL. Process and economic evaluation of the extraction and purification of recombinant beta-glucuronidase from transgenic corn. Biotechnol Prog 1998; 14(4): 607-14.
22. Mohseni MM, Amani J, Gheybi E, Salmanian AH. In silico analysis of chimeric subunit vaccine containing HER-2-MUC1 against breast cancer. IJBT 2018; 17(2):224-33.
23. Kahrizi D, Salmanian AH, Afshari A, Moieni A, Mousavi A. Simultaneous substitution of Gly96 to Ala and Ala183 to Thr in 5-enolpyruvylshikimate-3-phosphate synthase gene of E. coli (k12) and transformation of rapeseed (Brassica napus L.) in order to make tolerance to glyphosate. Plant Cell Rep 2007; 26(1):95-104.
24. DeBoer KD, Lye JC, Aitken CD, Su AK-K, Hamill JD. The A622 gene in Nicotiana glauca (tree tobacco): evidence for a functional role in pyridine alkaloid synthesis. Plant Mol Biol 2009; 69(3):299-312.
25. Kamada H, Okamura N, Satake M, Harada H, Shimomura K. Alkaloid production by hairy root cultures in Atropa belladonna. Plant Cell Rep 1986; 5(4):239-42.
26. Gheybi E, Amani J, Salmanian AH, Mashayekhi F, Khodi S. Designing a recombinant chimeric construct contain MUC1 and HER2 extracellular domain for prediagnostic breast cancer. Tumour Biol 2014; 35(11):11489-97.
27. Abkar M, Lotfi AS, Amani J, Eskandari K, Ramandi MF, Salimian J, et al. Survey of Omp19 immunogenicity against Brucella abortus and Brucella melitensis: influence of nanoparticulation versus traditional immunization. Vet Res Commun 2015; 39(4):217-28.
28. Du H, Yang X, Yan J, Li J. Fatty acid elongase 1 (FAE1) promoter as a candidate for genetic engineering of fatty acids to improve seed oil composition. African Journal of Biotechnology 2011; 10(84):19615-22.
29. Tiwari S, Verma PC, Singh PK, Tuli R. Plants as bioreactors for the production of vaccine antigens. Biotechnol Adv 2009; 27(4):449-67.
30. De Giovanni C, Nicoletti G, Quaglino E, Landuzzi L, Palladini A, Ianzano ML, et al. Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER-2. Breast Cancer Res 2014; 16(1):R10.
31. Shariat S, Badiee A, Jaafari MR, Mortazavi SA. Optimization of a Method to Prepare Liposomes Containing HER2/Neu-Derived Peptide as a Vaccine Delivery System for Breast Cancer. Iran J Pharm Res 2014; 13(Suppl):15-25.
32. Mittendorf EA, Peoples GE. Injecting hope--a review of breast cancer vaccines. Oncology 2016; 30(5):475-81.
33. Komarova TV, Kosorukov VS, Frolova OY, Petrunia IV, Skrypnik KA, Gleba YY, et al. Plant-made trastuzumab (herceptin) inhibits HER2/Neu+ cell proliferation and retards tumor growth. PloS one 2011; 6(3):e17541.
34. Laere E, Ling APK, Wong YP, Koh RY, Lila M, Azmi M, et al. Plant-based vaccines: Production and challenges. Journal of Botany 2016; 2016.
35. Huang Z-H, Shi L, Ma J-W, Sun Z-Y, Cai H, Chen Y-X, et al. A totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine for cancer therapy. J Am Chem Soc 2012; 134(21):8730-3.
36. Limacher J-M, Quoix E. TG4010: A therapeutic vaccine against MUC1 expressing tumors. Oncoimmunology 2012; 1(5):791-2.
37. Palitzsch B, Gaidzik N, Stergiou N, Stahn S, Hartmann S, Gerlitzki B, et al. A synthetic glycopeptide vaccine for the induction of a monoclonal antibody that differentiates between normal and tumor mammary cells and enables the diagnosis of human pancreatic cancer. Angew Chem Int Ed Engl 2016; 55(8):2894-8.
38. Pinkhasov J, Alvarez ML, Rigano MM, Piensook K, Larios D, Pabst M, et al. Recombinant plant‐expressed tumour‐associated MUC1 peptide is immunogenic and capable of breaking tolerance in MUC1. Tg mice. Plant Biotechnol J 2011; 9(9):991-1001.
39. Strasser R. Plant protein glycosylation. Glycobiology 2016; 26(9):926-39.
40. Gomord V, Fitchette A-C, Menu-Bouaouiche L, Saint-Jore-Dupas C, Plasson C, Michaud D, et al. Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol J 2010; 8(5):564-87.
41. Mikschofsky H, Schirrmeier H, Keil GM, Lange B, Polowick PL, Keller W, et al. Pea‐derived vaccines demonstrate high immunogenicity and protection in rabbits against rabbit haemorrhagic disease virus. Plant Biotechnol J 2009; 7(6):537-49.
42. Soria-Guerra RE, Rosales-Mendoza S, Márquez-Mercado C, López-Revilla R, Castillo-Collazo R, Alpuche-Solís ÁG. Transgenic tomatoes express an antigenic polypeptide containing epitopes of the diphtheria, pertussis and tetanus exotoxins, encoded by a synthetic gene. Plant Cell Rep 2007; 26(7):961-8.
43. Ahmad A, Pereira EO, Conley AJ, Richman AS, Menassa R. Green Biofactories: Recombinant Protein Production in Plants. Recent Pat Biotechnol 2010; 4(3):242-59.
44. Rybicki EP. Plant‐made vaccines for humans and animals. Plant Biotechnol J 2010; 8(5):620-37.
45. Mishra N, Gupta PN, Khatri K, Goyal AK, Vyas SP. Edible vaccines: A new approach to oral immunization. Indian J Biotechnol 2008; 7(3):283-94.
46. Appaiahgari MB, Kiran U, Ali A, Vrati S, Abdin MZ. Plant-Based Edible Vaccines: Issues and Advantages. Plant Biotechnology: Principles and Applications: Springer 2017:329-66.
47. Amani J, Mousavi SL, Rafati S, Salmanian AH. Immunogenicity of a plant-derived edible chimeric EspA, Intimin and Tir of Escherichia coli O157: H7 in mice. Plant Sci 2011; 180(4):620-7.
48. Li JT, Fei L, Mou ZR, Wei J, Tang Y, He HY, et al. Immunogenicity of a plant-derived edible rotavirus subunit vaccine transformed over fifty generations. Virology 2006; 356(1-2):171-8.
49. Yuki Y, Kiyono H. New generation of mucosal adjuvants for the induction of protective immunity. Rev Med Virol 2003; 13(5):293-310.
50. Jan N, Shafi F, Hameed O, Muzaffar K, Dar S, Majid I, et al. An Overview on Edible Vaccines and Immunization. Austin Journal of Nutrition and Food sciences 2016; 4:1078.
51. Fontenot JD, Tjandra N, Bu D, Ho C, Montelaro RC, Finn OJ. Biophysical characterization of one-, two-, and three-tandem repeats of human mucin (muc-1) protein core. Cancer Res 1993; 53(22):5386-94.
52. Ansel KM, Greenwald RJ, Agarwal S, Bassing CH, Monticelli S, Interlandi J, et al. Deletion of a conserved Il4 silencer impairs T helper type 1–mediated immunity. Nat Immunol 2004; 5(12):1251-9.
53. Zhang Y, Apilado R, Coleman J, Ben-Sasson S, Tsang S, Hu-Li J, et al. Interferon γ stabilizes the T helper cell type 1 phenotype. J Exp Med 2001; 194(2):165-72.
54. Jan N, Shafi F, bin Hameed O. An Overview on Edible Vaccines and Immunization. Austin J Nutri Food Sci 2016; 4(2):1078.
55. Smorlesi A, Papalini F, Orlando F, Donnini A, Re F, Provinciali M. Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma. Gene Ther 2005; 12(17):1324-32.
56. Lees CJ, Apostolopoulos V, McKenzie IF. Cytokine production from murine CD4 and CD8 cells after mannan-MUC1 immunization. J Interferon Cytokine Res 1999; 19(12):1373-9.
Published
2019-10-23
How to Cite
1.
Mehrab Mohseni M, Amani J, Fasihi Ramandi M, Mahjoubi F, Jafaria M, Salmanian AH. Immunogenicity Evaluation of Recombinant Edible Vaccine Candidate Containing HER2-MUC1 against Breast Cancer. Iran J Allergy Asthma Immunol. 18(5):511-522.
Section
Original Article(s)