Glycomodification and characterization of anti-colorectal cancer immunotherapeutic monoclonal antibodies in transgenic tobacco

作者: Yangkang So , Kyung-Jin Lee , Deuk-Su Kim , Jeong-Hwan Lee , Doo-Byoung Oh

DOI: 10.1007/S11240-012-0249-Z

关键词: ReceptorBiologyGlycosylationMonoclonal antibodyAntigenCD64KDELEndoplasmic reticulumAntibody-dependent cell-mediated cytotoxicityMolecular biology

摘要: Anti-colorectal cancer mAb CO17-1A (IgG2a) recognizes the antigen GA733, which is highly expressed on surface membrane of human colorectal carcinoma cells. In this study, a transgenic tobacco system for production was developed. The construct included KDEL sequence, an endoplasmic reticulum (ER) retention signal attached to C-terminus heavy chain, target accumulation into ER. An immunoblot showed significantly enhanced levels expression plant-derived mAbK (mAbPK) compared mAbP without sequence. ELISA assay using cells confirmed that mAbPK also higher than mAbP. Glycosylation analysis revealed had plant-specific glycans; whereas, primarily oligomannose glycans. FACS Fc domains both and mammalian-derived (mAbM) similar binding activity FcγRI receptor (CD64). However, slightly lower mAbM. antibody-dependent cell cytotoxicity mAbPK, against cells, as efficient mAbM; whereas very low. These results suggest localized accumulated in ER eventually with glycan anti-cancer biological parental

参考文章(40)
Kisung Ko, John L. Norelli, Jean-Paul Reynoird, Ewa Boresjza-Wysocka, Susan K. Brown, Herb S. Aldwinckle, Effect of untranslated leader sequence of AMV RNA 4 and signal peptide of pathogenesis-related protein 1b on attacin gene expression, and resistance to fire blight in transgenic apple Biotechnology Letters. ,vol. 22, pp. 373- 381 ,(2000) , 10.1023/A:1005672601625
Pablo Umaña, Joël Jean–Mairet, Radmila Moudry, Hanspeter Amstutz, James E. Bailey, Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity Nature Biotechnology. ,vol. 17, pp. 176- 180 ,(1999) , 10.1038/6179
Patrice Lerouge, Marion Cabanes-Macheteau, Catherine Rayon, Anne-Catherine Fischette-Lainé, Véronique Gomord, Loïc Faye, N-GLYCOPROTEIN BIOSYNTHESIS IN PLANTS : RECENT DEVELOPMENTS AND FUTURE TRENDS Plant Molecular Biology. ,vol. 38, pp. 31- 48 ,(1998) , 10.1007/978-94-011-5298-3_2
Alban J. Linnenbach, Dorothee Herlyn, Jan Zaloudik, Pierre Miniou, Yasushi Kasai, Christian P. Strassburg, Hilary Koprowski, Beth A. Seng, Baculovirus Recombinant Expressing a Secreted Form of a Transmembrane Carcinoma-associated Antigen Cancer Research. ,vol. 52, pp. 815- 821 ,(1992)
Larry Zeitlin, Stuart S. Olmsted, Thomas R. Moench, Man Sung Co, Brian J. Martinell, Vikram M. Paradkar, David R. Russell, Cary Queen, Richard A. Cone, Kevin J. Whaley, A humanized monoclonal antibody produced in transgenic plants for immunoprotection of the vagina against genital herpes Nature Biotechnology. ,vol. 16, pp. 1361- 1364 ,(1998) , 10.1038/4344
Luisa Bortesi, Marzia Rossato, Flora Schuster, Nicole Raven, Johannes Stadlmann, Linda Avesani, Alberto Falorni, Flavia Bazzoni, Ralph Bock, Stefan Schillberg, Mario Pezzotti, Viral and murine interleukin-10 are correctly processed and retain their biological activity when produced in tobacco. BMC Biotechnology. ,vol. 9, pp. 22- 22 ,(2009) , 10.1186/1472-6750-9-22
K. Ko, Y. Tekoah, P. M. Rudd, D. J. Harvey, R. A. Dwek, S. Spitsin, C. A. Hanlon, C. Rupprecht, B. Dietzschold, M. Golovkin, H. Koprowski, Function and glycosylation of plant-derived antiviral monoclonal antibody Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 8013- 8018 ,(2003) , 10.1073/PNAS.0832472100
Janet M. Sharp, Pauline M. Doran, Characterization of monoclonal antibody fragments produced by plant cells. Biotechnology and Bioengineering. ,vol. 73, pp. 338- 346 ,(2001) , 10.1002/BIT.1067