Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies.
This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 microg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries.
Stöger
E
E
John Innes Centre, Norwich Research Park, UK.
Vaquero
C
C
Torres
E
E
Sack
M
M
Nicholson
L
L
Drossard
J
J
Williams
S
S
Keen
D
D
Perrin
Y
Y
Christou
P
P
Fischer
R
R
D000818:Animals; D015153:Blotting, Western; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology; D002645:Chickens; D004355:Drug Stability; D004356:Drug Storage; D002523:Edible Grain / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics* / Q000276:immunology; D051379:Mice; D012275:Oryza / Q000235:genetics / Q000378:metabolism; D018515:Plant Leaves / Q000235:genetics / Q000378:metabolism; D030821:Plants, Genetically Modified; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012639:Seeds / Q000235:genetics / Q000378:metabolism; D014908:Triticum / Q000235:genetics / Q000378:metabolism
D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D011993:Recombinant Fusion Proteins; C055966:immunoglobulin Fv