Plant-derived PAP proteins fused to immunoglobulin A and M Fc domains induce anti-prostate cancer immune response in mice
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
In this study, recombinant Fc-fused Prostate acid phosphatase(PAP) proteins were produced in transgenic plants. PAP was fusedto immunoglobulin (Ig) A and M Fc domain (PAP-IgA Fc andPAP-IgM Fc), which were tagged to the ER retention sequenceKDEL to generate PAP-IgA FcK and PAP-IgM FcK. Agrobacteriummediatedtransformation was performed to produce transgenictobacco plants expressing four recombinant proteins. GenomicPCR and RT-PCR analyses confirmed the transgene insertionand mRNA transcription of PAP-IgA Fc, PAP-IgM Fc, PAP-IgAFcK, and PAP-IgM FcK in tobacco plant leaves. Western blotconfirmed the expression of PAP-IgA Fc, PAP-IgM Fc, PAP-IgAFcK, and PAP-IgM FcK proteins. SEC-HPLC and Bio-TEM analyseswere performed to confirm the size and shape of the plant-derivedrecombinant PAP-Fc fusion proteins. In mice experiments,the plant-derived IgA and IgM Fc fused proteins induced productionof total IgGs including IgG1 against PAP. This resultsuggests that IgA and IgM Fc fusion can be applied to producerecombinant PAP proteins as a prostate cancer vaccine in plantexpression system.
Abstract
In this study, recombinant Fc-fused Prostate acid phosphatase(PAP) proteins were produced in transgenic plants. PAP was fusedto immunoglobulin (Ig) A and M Fc domain (PAP-IgA Fc andPAP-IgM Fc), which were tagged to the ER retention sequenceKDEL to generate PAP-IgA FcK and PAP-IgM FcK. Agrobacteriummediatedtransformation was performed to produce transgenictobacco plants expressing four recombinant proteins. GenomicPCR and RT-PCR analyses confirmed the transgene insertionand mRNA transcription of PAP-IgA Fc, PAP-IgM Fc, PAP-IgAFcK, and PAP-IgM FcK in tobacco plant leaves. Western blotconfirmed the expression of PAP-IgA Fc, PAP-IgM Fc, PAP-IgAFcK, and PAP-IgM FcK proteins. SEC-HPLC and Bio-TEM analyseswere performed to confirm the size and shape of the plant-derivedrecombinant PAP-Fc fusion proteins. In mice experiments,the plant-derived IgA and IgM Fc fused proteins induced productionof total IgGs including IgG1 against PAP. This resultsuggests that IgA and IgM Fc fusion can be applied to producerecombinant PAP proteins as a prostate cancer vaccine in plantexpression system.
참고문헌 (39)
- Barve A, "Prostate cancer relevant antigens and enzymes for targeted drug delivery", J Control Release, 187, pp.118~132 (2014)
- Quintero IB, "Prostatic acid phosphatase is not a prostate specific target", Cancer Res, 67, pp.6549~6554 (2007)
- 권순석, "Updates on cancer epidemiology in Korea, 2018", 전남의대학술지, 54(2), pp.90~100 (2018), 의과학연구소[DOI]
- Zhang H, "Current status and future directions of cancer immunotherapy", J Cancer, 9, pp.1773~1781 (2018)
- Sharma P, "Primary, adaptive, and acquired resistance to cancer immunotherapy", Cell, 168, pp.707~723 (2017)
- Rius M, "Epigenetic cancer therapy : rationales, targets and drugs", Oncogene, 31, pp.4257~4265 (2012)
- Petrylak DP, "Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer", N Engl J Med, 351, pp.1513~1520 (2004)
- Yang C, "Engineering of fc fragments with optimized physicochemical properties implying improvement of clinical potentials for fc-based therapeutics", Front Immunol, 8, pp.1860~ (2018)
- Czajkowsky DM, "Fcfusion proteins : new developments and future perspectives", EMBO Mol Med, 4, pp.1015~1028 (2012)
- Korhonen R, "Abatacept, a novel CD80", 86-CD28 T cell co-stimulation modulator, in the treatment of rheumatoid arthritis, 2009, pp.104, 276~284
- Cines DB, "Romiplostim", Nat Rev Drug Discov, 7, pp.887~888 (2008)
- Strober BE, "Alefacept for the treatment of psoriasis and other dermatologic diseases", Dermatol Ther, 20, pp.270~276 (2007)
- Ammann JU, "Detection of weak receptor-ligand interactions using IgM and J-chain-based fusion proteins", Eur J Immunol, 42, pp.1354~1356 (2012)
- Nagashima H, "TNF receptor II fusion protein with tandemly repeated Fc domains", J Biochem, 149, pp.337~346 (2011)
- Mekhaiel DNA, "Polymeric human Fc-fusion proteins with modified effector functions", Sci Rep, 1, pp.124~124 (2011)
- Heller JE, "Prostatic acid phosphatase : its current clinical status", J Urol, 137, pp.1091~1103 (1987)
- Guenzi S, "The efficiency of cysteine-mediated intracellular retention determines the differential fate of secretory IgA and IgM in B and plasma cells", Eur J Immunol, 24, pp.2477~2482 (1994)
- Davis AC, "On the structure of polymeric IgM", Eur J Immunol, 18, pp.1001~1008 (1988)
- Lim Chae-Yeon, "Immune Responses to Plant-Derived Recombinant Colorectal Cancer Glycoprotein EpCAM-FcK Fusion Protein in Mice", Biomolecules & Therapeutics, 30(6), pp.546~552 (2022), 한국응용약물학회[DOI]
- 송일찬, "Expression and in vitro function of anti-cancer mAbs in transgenic Arabidopsis thaliana", BMB Reports, 53(4), pp.229~233 (2020), 생화학분자생물학회[DOI]
- Kim DS, "A plant-derived antigen-antibody complex induces anti-cancer immune responses by forming a large quaternary structure", Int J Mol Sci, 21, pp.1~18 (2020)
- Song I, "Endoplasmic reticulum retention motif fused to recombinant anti-cancer monoclonal antibody(mAb)CO17-1A affects mAb expression and plant stress response", PloS One, 13, pp.e0198978~ (2018)
- Fischer R, "Towards molecular farming in the future : transient protein expression in plants", Biotechnol Appl Biochem, 30(Pt 2), pp.113~116 (1999)
- Fischer R, "Towards molecular farming in the future : moving from diagnostic protein and antibody production in microbes to plants", Biotechnol Appl Biochem, 30(Pt 2), pp.101~108 (1999)
- Shanmugaraj BM, "Plant expression platform for the production of recombinant pharmaceutical proteins", Austin J Biotechnol Bioeng, 1, pp.4~ (2014)
- Horn M, "Plant molecular farming : systems and products", Plant Cell Rep, 22, pp.711~720 (2004)
- Twyman RM, "Molecular farming in plants : host systems and expression technology", Trends Biotechnol, 21, pp.570~578 (2003)
- Lim CY, "Effect of the developmental stage and tissue position on the expression and glycosylation of recombinant glycoprotein GA733-FcK in transgenic plants", Front Plant Sci, 5, pp.778~ (2015)
- Lu Z, "Expression of GA733-Fc fusion protein as a vaccine candidate for colorectal cancer in transgenic plants", Biomed Res Int, 2012, pp.364240~ (2012)
- Schouten A, "The C-terminal KDEL sequence increases the expression level of a single-chain antibody designed to be targeted to both the cytosol and the secretory pathway in transgenic tobacco", Plant Mol Biol, 30, pp.781~793 (1996)
- Wandelt CI, "Vicilin with carboxy-terminal KDEL is retained in the endoplasmic reticulum and accumulates to high levels in the leaves of transgenic plants", Plant J, 2, pp.181~192 (1992)
- Schroeder HW Jr, "Structure and function of immunoglobulins", J Allergy Clin Immunol, 125, pp.S41~S52 (2010)
- Sorensen V, "Polymerization of IgA and IgM : roles of Cys309", Cys414 and the secretory tailpiece, 1999, pp.162, 3448~3455
- Normansell DE, "Human immunoglobulin subclasses", Diagn Clin Immunol, 5, pp.115~128 (1987)
- Kartikasari AER, "Therapeutic cancer vaccines-T cell responses and epigenetic modulation", Front Immunol, 9, pp.3109~ (2019)
- Westdorp H, "Immunotherapy for prostate cancer : lessons from responses to tumor-associated antigens", Front Immunol, 5, pp.191~ (2014)
- Melssen M, "Vaccines targeting helper T cells for cancer immunotherapy", Curr Opin Immunol, 47, pp.85~92 (2017)
- GRGina R. Webster, "A polymeric immunoglobulin-antigen fusion protein strategy for enhancing vaccine immunogenicity", Plant Biotechnol J, 16, pp.1983~1996 (2018)
- Shanmugaraj B, "Plant molecular farming : a viable platform for recombinant biopharmaceutical production", Plants, 9, pp.842~ (2020)
