Production of human monoclonal antibody in eggs of chimeric chickens.
The tubular gland of the chicken oviduct is an attractive system for protein expression as large quantities of proteins are deposited in the egg, the production of eggs is easily scalable and good manufacturing practices for therapeutics from eggs have been established. Here we examined the ability of upstream and downstream DNA sequences of ovalbumin, a protein produced exclusively in very high quantities in chicken egg white, to drive tissue-specific expression of human mAb in chicken eggs. To accommodate these large regulatory regions, we established and transfected lines of chicken embryonic stem (cES) cells and formed chimeras that express mAb from cES cell-derived tubular gland cells. Eggs from high-grade chimeras contained up to 3 mg of mAb that possesses enhanced antibody-dependent cellular cytotoxicity (ADCC), nonantigenic glycosylation, acceptable half-life, excellent antigen recognition and good rates of internalization.
Zhu
Lei
L
Origen Therapeutics, 1450 Rollins Road, Burlingame, California 94010, USA.
van de Lavoir
Marie-Cecile
MC
Albanese
Jenny
J
Beenhouwer
David O
DO
Cardarelli
Pina M
PM
Cuison
Severino
S
Deng
David F
DF
Deshpande
Shrikant
S
Diamond
Jennifer H
JH
Green
Lynae
L
Halk
Edward L
EL
Heyer
Babette S
BS
Kay
Robert M
RM
Kerchner
Allyn
A
Leighton
Philip A
PA
Mather
Christine M
CM
Morrison
Sherie L
SL
Nikolov
Zivko L
ZL
Passmore
David B
DB
Pradas-Monne
Alicia
A
Preston
Benjamin T
BT
Rangan
Vangipuram S
VS
Shi
Mingxia
M
Srinivasan
Mohan
M
White
Steven G
SG
Winters-Digiacinto
Peggy
P
Wong
Susan
S
Zhou
Wen
W
Etches
Robert J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D015139:Blotting, Southern; D015153:Blotting, Western; D016466:CHO Cells; D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry; D002645:Chickens; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004529:Egg White; D004622:Embryo, Mammalian / Q000166:cytology; D004625:Embryo, Nonmammalian; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D016678:Genome; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G; D007150:Immunohistochemistry; D007525:Isoelectric Focusing; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D009005:Monosaccharides / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry; D010047:Ovalbumin / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D013234:Stem Cells / Q000166:cytology
D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D007074:Immunoglobulin G; D009005:Monosaccharides; D009844:Oligosaccharides; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin; D004247:DNA