Monoclonal antibodies produced by muscle after plasmid injection and electroporation.
Antibodies are useful for the treatment of a variety of diseases. We here demonstrate that mouse muscle produced monoclonal antibodies (mAb) after a single injection of immunoglobulin genes as plasmid DNA. In vivo electroporation of muscle greatly enhanced antibody production. For chimeric antibodies, levels of 50-200 ng mAb/ml serum were obtained but levels declined after 7-14 days due to an immune response against the xenogeneic parts of the antibody. By contrast, fully mouse antibodies persisted in serum for at least 7 months. mAb produced by the muscle had correct structure, specificity, and biological effector functions. The findings were extended to a larger animal, the sheep, in which mAb serum levels of 30-50 ng/ml were obtained. Sustained levels of serum mAb, induced by single injection of Ig genes and electroporation of muscle cells, may offer significant advantages in the treatment of human diseases.
Tjelle
Torunn Elisabeth
TE
Inovio AS, Forskningsveien 2a, 0373 Oslo, Norway. t.e.tjelle@inovio.com
Corthay
Alexandre
A
Lunde
Elin
E
Sandlie
Inger
I
Michaelsen
Terje E
TE
Mathiesen
Iacob
I
Bogen
Bjarne
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003167:Complement Activation; D003165:Complement System Proteins; D004247:DNA / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D018274:Electroporation / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015151:Immunoblotting; D007136:Immunoglobulins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism*; D012756:Sheep; D013154:Spleen / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D003165:Complement System Proteins; D004247:DNA