Tumor targeting of humanized fragment antibody secreted from transgenic rice cell suspension culture.
The tumor-associated glycoprotein 72 (TAG 72) has been shown to be expressed in the majority of human adenocarcinomas. In an effort to develop a technique for the safe and inexpensive production of large quantities of anti-TAG 72 humanized antibody fragments (hzAb) as a future source of clinical-grade proteins, we developed a transgenic rice cell suspension culture system. The in vivo assembly and secretion of hzAb were achieved in a transgenic rice cell culture under the control of the rice alpha amylase 3D (RAmy 3D) expression system, and the biological activities of plant-derived hzAb were determined to be quite similar to those of animal-derived antibody. Purified hzAb was shown to bind to the recombinant antigen, TAG 72, and to bind specifically to human LS 174T colon adenocarcinoma cells expressing the TAG 72 antigen, and this binding occurred to the same extent as was seen with animal-derived antibody. Plant-derived hzAb proved as effective as animal-derived antibody in targeting tumors of xenotransplanted LS 174T cells in nude mice. The results of this study indicate that the hzAb derived from plant cell suspension cultures may have great potential for pharmaceutical applications in the development of future cancer therapeutic and diagnostic protocols.
Hong
Shin-Young
SY
Division of Biological Sciences, Research Institute for Bioactive Materials, Chonbuk National University, Jeonju 561-756, Korea.
Lee
Tae-Sup
TS
Kim
Ju
J
Jung
Jae-Ho
JH
Choi
Chang-Woon
CW
Kim
Tae-Geum
TG
Kwon
Tae-Ho
TH
Jang
Yong-Suk
YS
Yang
Moon-Sik
MS
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015153:Blotting, Western; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D012275:Oryza / Q000166:cytology* / Q000235:genetics*; D030821:Plants, Genetically Modified; D011485:Protein Binding; D013347:Subcellular Fractions / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000951:Antigens, Neoplasm; D003470:Culture Media; D006023:Glycoproteins; D007128:Immunoglobulin Fragments; D009077:Mucins; C047052:tumor-associated antigen 72