High level expression of a functional human/mouse chimeric anti-CD20 monoclonal antibody in milk of transgenic mice.
Rituximab, a chimeric anti-CD20 monoclonal antibody, is one of the most successful biomedicines and has been used to treat at least 370,000 patients with indolent, aggressive non-Hodgkin's lymphoma and other malignant diseases. However, the global demand for rituximab and other therapeutic monoclonal antibodies is exponentially increasing and barely able to be met by current manufacturing capacities of mammalian cell culture. The mammary gland bioreactor has been regarded as an ideal substitute for mammalian cell culture to mass-produce recombinant monoclonal antibodies at the lowest possible cost. Here, we show a feasible model to produce recombinant anti-CD20 antibodies in the mammary glands of transgenic animals. Six lines of transgenic mice were generated by co-microinjection of the two expression cassettes that can specially express the chimeric light and heavy chain of anti-CD20 mAbs in the milk of transgenic animals. The recombinant antibodies were detected in the milk of transgenic mice with the highest expression level up to 17 microg/mul and could specifically bind the CD20 surface antigens on human B-lymphoma cells.
Tang
Bo
B
State Key Lab for Agrobiotechnology, China Agricultural University, Yuanmingyuan West Road 2, Haidian District, Beijing, China.
Yu
Shanshan
S
Zheng
Min
M
Ding
Fangrong
F
Zhao
Rui
R
Zhao
Jianmin
J
Dai
Yunping
Y
Li
Ning
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D018951:Antigens, CD20 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000276:immunology* / Q000378:metabolism*; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D000069283:Rituximab