In vitro and in vivo secretion of cloned antibodies by genetically modified myogenic cells.
In vivo production of recombinant antibodies by engineered cells may have applications for gene therapy of certain cancers and of certain severe viral diseases. It would also permit the development of new animal models of autoimmune diseases and new approaches for in vivo ablation of specific cell types for fundamental purposes. Using gene transfer of an anti-human thyroglobulin monoclonal antibody, we show here that several cell types permitting autologous grafting of genetically engineered cells are efficiently able to secrete antibodies in vitro. Those cells include skin fibroblasts, hepatocytes, and myogenic cells. We also show that the secreted antibodies display an affinity for the antigen close to that of the parental antibody, with, however, slight differences varying according to the cell type. This indicates that the foldings of antigen combining sites of antibodies produced in B cell- and non-B cell contexts are very similar. Finally, we report that, when implanted in the forelimb of a mouse, genetically modified myogenic cells are able to secrete antibodies for at least 4 months. Taken together, our observations point to the notion that genetic modification of patient cells may be used for long-term antibody-based gene therapies.
Noël
D
D
Institut de Génétique Moléculaire de Montpellier, UMR 5535, Montpellier, France.
Pelegrin
M
M
Marin
M
M
Biard-Piechaczyk
M
M
Ourlin
J C
JC
Mani
J C
JC
Piechaczyk
M
M
D000818:Animals; D000906:Antibodies / Q000235:genetics* / Q000378:metabolism*; D017690:Cell Transplantation; D005347:Fibroblasts / Q000276:immunology; D005552:Forelimb / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000166:cytology* / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D012867:Skin / Q000166:cytology; D013954:Thyroglobulin / Q000276:immunology
D000906:Antibodies; D011994:Recombinant Proteins; D013954:Thyroglobulin