Structure of PAP-IgM FcK fusion protein with J-chain expressed in transgenic plant

Kang, Yangjoo; Kim, Deuk-Su; Kim, Kibum; Myung, Soon-Chul; Oh, Yoo Jin; Park, Sungsu; Hinterdorfer, Peter; Ko, Kisung

doi:10.2478/ebtj-2023-0006

Abstract

Transgenic plants expressing immunoglobulin (Ig) M Fc-fused Prostate acid phosphatase (PAP) antigenic proteins (PAP-IgM FcK) and J-chain proteins were generated by Agrobacterium-mediated transformation. The Fc region was tagged with the ER retention motif (KDEL) to make PAP-IgM FcK. Two transgenic plants were crossed together to generate F₁ expressing both PAP-IgM FcK and J-chain proteins (PAP-IgM FcK × J-chain). PCR and RT-PCR analyses confirmed the transgene insertion and mRNA transcription of PAP-IgM FcK and J-chain in leaf tissue of PAP-IgM FcK × J-chain F₁ plant. Western blot confirmed the expression of PAP-IgM FcK × J-chain protein. Size exclusion (SEC)-high performance liquid chromatography (HPLC) and Bio-transmission electron microscope (TEM) analyses were performed to show the size and shape of the PAP- IgM FcK × J-chain fusion proteins. These results suggest that PAP-IgM FcK with J-chain can be produced in plant expression system with plant crossing.

References

1. Brandtzaeg, P., and Prydz, H. (1984). Direct evidence for an integrated function of J chain and secretory component in epithelial transport of immunoglobulins. Nature 311, 71.10.1038/311071a06433206
Search in Google Scholar Back to article
2. Cines, D.B., Yasothan, U., and Kirkpatrick, P. (2008). Romiplostim. Nature Reviews Drug Discovery 7, 887.10.1038/nrd274118974747
Search in Google Scholar Back to article
3. Di Lorenzo, G., Ferro, M., and Buonerba, C. (2012). Sipuleucel-T (Provenge®) for castration-resistant prostate cancer. BJU International 110, E99-E104.10.1111/j.1464-410X.2011.10790.x22177289
Search in Google Scholar Back to article
4. Fong, L., Brockstedt, D., Benike, C., Breen, J.K., Strang, G., Ruegg, C.L., and Engleman, E.G. (2001). Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy. J Immunol 167, 7150-7156.10.4049/jimmunol.167.12.715011739538
Search in Google Scholar Back to article
5. Fong, L., Ruegg, C.L., Brockstedt, D., Engleman, E.G., and Laus, R. (1997). Induction of tissue-specific autoimmune prostatitis with prostatic acid phosphatase immunization: implications for immunotherapy of prostate cancer. J Immunol 159, 3113-3117.10.4049/jimmunol.159.7.3113
Search in Google Scholar Back to article
6. Fujio, K., Watanabe, M., Ueki, H., Li, S.A., Kinoshita, R., Ochiai, K., Futami, J., Watanabe, T., Nasu, Y., and Kumon, H. (2015). A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment. Oncol Rep 33, 1585-1592.10.3892/or.2015.3770435808025632844
Search in Google Scholar Back to article
7. Hiramoto, E., Tsutsumi, A., Suzuki, R., Matsuoka, S., Arai, S., Kikkawa, M., and Miyazaki, T. (2018). The IgM pen-tamer is an asymmetric pentagon with an open groove that binds the AIM protein. Science Advances 4, eaau1199.10.1126/sciadv.aau1199617937930324136
Search in Google Scholar Back to article
8. Johansen, F.E., Braathen, R., and Brandtzaeg, P. (2000). Role of J chain in secretory immunoglobulin formation. Scand J Immunol 52, 240-248.10.1046/j.1365-3083.2000.00790.x10972899
Search in Google Scholar Back to article
9. Kang, Y.J., Kim, D.-S., Myung, S.-C., and Ko, K. (2017). Expression of a Human Prostatic Acid Phosphatase (PAP)-IgM Fc Fusion Protein in Plants Using In vitro Tissue Subculture. Frontiers in Plant Science 8.10.3389/fpls.2017.00274532901628293250
Search in Google Scholar Back to article
10. Kantoff, P.W., Higano, C.S., Shore, N.D., Berger, E.R., Small, E.J., Penson, D.F., Redfern, C.H., Ferrari, A.C., Dreicer, R., Sims, R.B., Xu, Y., Frohlich, M.W., and Schellhammer, P.F. (2010). Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363, 411-422.10.1056/NEJMoa100129420818862
Search in Google Scholar Back to article
11. Kim, K., Kang, Y.J., Park, S.R., Kim, D.-S., Lee, S.-W., Ko, K., Ponndorf, D., and Ko, K. (2021). Effect of leaf position and days post-infiltration on transient expression of colorectal cancer vaccine candidate proteins GA733-Fc and GA733-FcK in Nicotiana benthamiana plant. PeerJ 9, e10851.10.7717/peerj.10851803589933868796
Search in Google Scholar Back to article
12. Korhonen, R., and Moilanen, E. (2009). Abatacept, a Novel CD80/86–CD28 T Cell Co-stimulation Modulator, in the Treatment of Rheumatoid Arthritis. Basic & Clinical Pharmacology & Toxicology 104, 276-284.10.1111/j.1742-7843.2009.00375.x19228144
Search in Google Scholar Back to article
13. Krugmann, S., Pleass, R.J., Atkin, J.D., and Woof, J.M. (1997). Structural requirements for assembly of dimeric IgA probed by site-directed mutagenesis of J chain and a cysteine residue of the alpha-chain CH2 domain. J Immunol 159, 244-249.10.4049/jimmunol.159.1.244
Search in Google Scholar Back to article
14. Kuter, D.J., Bussel, J.B., Lyons, R.M., Pullarkat, V., Gernsheimer, T.B., Senecal, F.M., Aledort, L.M., George, J.N., Kessler, C.M., Sanz, M.A., Liebman, H.A., Slovick, F.T., De Wolf, J.T., Bourgeois, E., Guthrie, T.H., Jr., Newland, A., Wasser, J.S., Hamburg, S.I., Grande, C., Lefrere, F., Lichtin, A.E., Tarantino, M.D., Terebelo, H.R., Viallard, J.F., Cuevas, F.J., Go, R.S., Henry, D.H., Redner, R.L., Rice, L., Schipperus, M.R., Guo, D.M., and Nichol, J.L. (2008). Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 371, 395-403.10.1016/S0140-6736(08)60203-218242413
Search in Google Scholar Back to article
15. Lai, T., Yang, Y., and Ng, S.K. (2013). Advances in Mammalian cell line development technologies for recombinant protein production. Pharmaceuticals (Basel) 6, 579-603.10.3390/ph6050579381772424276168
Search in Google Scholar Back to article
16. Lim, C.-Y., Kim, D.-S., Kang, Y., Lee, Y.-R., Kim, K., Kim, M.-S., and Ko, K. (2022). Immune Responses to Plant-Derived Recombinant Colorectal Cancer Glycoprotein Ep-CAM-FcK Fusion Protein in Mice. Biomolecules & Therapeutics 30, 546-552.10.4062/biomolther.2022.103962231536263857
Search in Google Scholar Back to article
17. Linderholm, A., and Chamow, S. (2014). Immunoglobulin Fc-fusion proteins part 2: therapeutic uses and clinical development. Bioprocess Int. 2014b 12, 2-7.
Search in Google Scholar Back to article
18. Machlenkin, A., Paz, A., Haim, E.B., Goldberger, O., Finkel, E., Tirosh, B., Volovitz, I., Vadai, E., Lugassy, G., and Cytron, S. (2005). Human CTL epitopes prostatic acid phosphatase-3 and six-transmembrane epithelial antigen of prostate-3 as candidates for prostate cancer immuno-therapy. Cancer research 65, 6435-6442.10.1158/0008-5472.CAN-05-013316024648
Search in Google Scholar Back to article
19. Matsueda, S., Takedatsu, H., Yao, A., Tanaka, M., Noguchi, M., Itoh, K., and Harada, M. (2005). Identification of peptide vaccine candidates for prostate cancer patients with HLA-A3 supertype alleles. Clinical cancer research 11, 6933-6943.10.1158/1078-0432.CCR-05-068216203785
Search in Google Scholar Back to article
20. Mcneel, D.G., Dunphy, E.J., Davies, J.G., Frye, T.P., Johnson, L.E., Staab, M.J., Horvath, D.L., Straus, J., Alberti, D., and Marnocha, R. (2009). Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer. Journal of Clinical Oncology 27, 4047.10.1200/JCO.2008.19.9968273441819636017
Search in Google Scholar Back to article
21. Milstein, C.P., Richardson, N.E., Dieverson, E.V., and Feinstein, A. (1975). Interchain disulphide bridges of mouse immunoglobulin M. The Biochemical journal 151, 615-624.10.1042/bj15106151172409766753
Search in Google Scholar Back to article
22. Peshwa, M.V., Shi, J.D., Ruegg, C., Laus, R., and Van Schooten, W.C.A. (1998). Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using antigen-presenting cells pulsed with prostatic acid phosphatase peptide. The Prostate 36, 129-138.10.1002/(SICI)1097-0045(19980701)36:2<129::AID-PROS8>3.0.CO;2-D
Search in Google Scholar Back to article
23. Peters, R.T., Low, S.C., Kamphaus, G.D., Dumont, J.A., Amari, J.V., Lu, Q., Zarbis-Papastoitsis, G., Reidy, T.J., Merricks, E.P., Nichols, T.C., and Bitonti, A.J. (2010). Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood 115, 2057-2064.10.1182/blood-2009-08-239665
Search in Google Scholar Back to article
24. Powell, J.S., Josephson, N.C., Quon, D., Ragni, M.V., Cheng, G., Li, E., Jiang, H., Li, L., Dumont, J.A., Goyal, J., Zhang, X., Sommer, J., Mccue, J., Barbetti, M., Luk, A., and Pierce, G.F. (2012). Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood 119, 3031-3037.10.1182/blood-2011-09-382846
Search in Google Scholar Back to article
25. Randall, T.D., Brewer, J.W., and Corley, R.B. (1992). Direct evidence that J chain regulates the polymeric structure of IgM in antibody-secreting B cells. J Biol Chem 267, 18002-18007.10.1016/S0021-9258(19)37143-1
Search in Google Scholar Back to article
26. Rasooly, R., Hernlem, B., and Friedman, M. (2013). Low levels of aflatoxin B1, ricin, and milk enhance recombinant protein production in mammalian cells. PloS one 8, e71682-e71682.10.1371/journal.pone.0071682
Search in Google Scholar Back to article
27. Roos, A.K., Pavlenko, M., Charo, J., Egevad, L., and Pisa, P. (2005). Induction of PSA-specific CTLs and anti-tumor immunity by a genetic prostate cancer vaccine. The Prostate 62, 217-223.10.1002/pros.20135
Search in Google Scholar Back to article
28. Roux, K.H. (1999). Immunoglobulin structure and function as revealed by electron microscopy. Int Arch Allergy Immunol 120, 85-99.10.1159/000024226
Search in Google Scholar Back to article
29. Saif, J.M.S., Vadakekolathu, J., Rane, S.S., Mcdonald, D., Ahmad, M., Mathieu, M., Pockley, A.G., Durrant, L., Metheringham, R., Rees, R.C., and Mcardle, S.E.B. (2014). Novel prostate acid phosphatase-based peptide vaccination strategy induces antigen-specific T-cell responses and limits tumour growth in mice. European Journal of Immunology 44, 994-1004.10.1002/eji.201343863
Search in Google Scholar Back to article
30. Shanmugaraj, B.M., and Ramalingam, S. (2014). Plant expression platform for the production of recombinant pharmaceutical proteins. Austin J Biotechnol Bioeng 1, 4.
Search in Google Scholar Back to article
31. Sorensen, V., Sundvold, V., Michaelsen, T.E., and Sandlie, I. (1999). Polymerization of IgA and IgM: roles of Cys309/Cys414 and the secretory tailpiece. J Immunol 162, 3448-3455.10.4049/jimmunol.162.6.3448
Search in Google Scholar Back to article
32. Strober, B.E., and Menon, K. (2007). Alefacept for the treatment of psoriasis and other dermatologic diseases. Dermatol Ther 20, 270-276.10.1111/j.1529-8019.2007.00140.x
Search in Google Scholar Back to article
33. Vaerman, J.P., Langendries, A.E., Giffroy, D.A., Kaetzel, C.S., Fiani, C.M., Moro, I., Brandtzaeg, P., and Kobayashi, K. (1998). Antibody against the human J chain inhibits polymeric Ig receptor-mediated biliary and epithelial transport of human polymeric IgA. Eur J Immunol 28, 171-182.10.1002/(SICI)1521-4141(199801)28:01<171::AID-IMMU171>3.0.CO;2-#
Search in Google Scholar Back to article
34. Van Den Brande, J.M., Braat, H., Van Den Brink, G.R., Versteeg, H.H., Bauer, C.A., Hoedemaeker, I., Van Montfrans, C., Hommes, D.W., Peppelenbosch, M.P., and Van Deventer, S.J. (2003). Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn’s disease. Gastroenterology 124, 1774-1785.10.1016/S0016-5085(03)00382-2
Search in Google Scholar Back to article
35. Wiersma, E.J., Collins, C., Fazel, S., and Shulman, M.J. (1998). Structural and functional analysis of J chain-deficient IgM. J Immunol 160, 5979-5989.10.4049/jimmunol.160.12.5979
Search in Google Scholar Back to article
36. Woof, J.M., and Russell, M.W. (2011). Structure and function relationships in IgA. Mucosal Immunol 4, 590-597.10.1038/mi.2011.39
Search in Google Scholar Back to article

Structure of PAP-IgM FcK fusion protein with J-chain expressed in transgenic plant

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