Systemic long-term delivery of antibodies in immunocompetent animals using cellulose sulphate capsules containing antibody-producing cells.
Implantation of capsules containing antibody-producing cells into patients would potentially permit systemic long-term delivery of antibodies and might, thus, be useful in the development of surveillance treatments for cancers and severe viral diseases. We show that cellulose sulphate (CS) capsules containing hybridoma cells, when implanted subcutaneously or in the intraperitoneal cavity, can be used for delivering monoclonal antibodies into the blood-stream of immunocompetent mice for at least several months. In contrast to capsules implanted into the intraperitoneal cavity, which remain mobile and nonvascularized, capsules implanted under the skin form neo-organs which become vascularized within days. This may explain the higher blood concentration of the antibody we have observed in the latter case. Importantly, neither an isolating fibrosis nor an obvious inflammatory response was detected at the capsule implantation sites during observation periods as long as 10 months. Finally, no anti-idiotypic immune response against the ectopically delivered antibody was shown to occur. This rules out any potent adjuvant effect of the cellulose sulphate matrix that might have stimulated a neutralizing humoral response. Taken together, our data indicate that encapsulation of antibody-producing cells into CS might be used in antibody-based gene/cell therapy approaches.
Pelegrin
M
M
Institut de Génétique Moléculaire de Montpellier, UMR 5535/IFR 24, France.
Marin
M
M
Noël
D
D
Del Rio
M
M
Saller
R
R
Stange
J
J
Mitzner
S
S
Günzburg
W H
WH
Piechaczyk
M
M
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000921:Antibody-Producing Cells; D002482:Cellulose / Q000031:analogs & derivatives*; D004343:Drug Implants; D004797:Enzyme-Linked Immunosorbent Assay; D006825:Hybridomas; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D009389:Neovascularization, Pathologic
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D004343:Drug Implants; D002482:Cellulose; C020254:cellulose sulfate