Cytomedical therapy for IgG1 plasmacytosis in human interleukin-6 transgenic mice using hybridoma cells microencapsulated in alginate-poly(L)lysine-alginate membrane.
Cytomedical therapy for human interleukin-6 transgenic mice (hIL-6 Tgm) was implemented by the intraperitoneal injection of alginate-poly(L)lysine-alginate (APA) membranes microencapsulating SK2 hybridoma cells (APA-SK2 cells) which secrete anti-hIL-6 monoclonal antibodies (SK2 mAb). IgG1 plasmacytosis in the hIL-6 Tgm was suppressed by a single injection of APA-SK2 cells, and the survival time of these mice was remarkably prolonged. The viable cell number and the SK2 mAb-secretion of APA-SK2 cells increased for at least one month both under culture conditions and in allogeneic recipients (in vivo). Moreover, SK2 mAb which were secreted from APA-SK2 cells injected into allogeneic recipients was detected in serum at high concentrations; 3-5 mg/ml from day 14 to day 50 post-injection. In contrast, the injection of free SK2 cells had no therapeutic effect on hIL-6 Tgm. These results strongly suggest that APA membranes microencapsulating cells which were modified to secrete molecules useful for the treatment of a disorder were effective as an in vivo long-term delivery system of bioactive molecules, as 'cytomedicine'.
Okada
N
N
Faculty and Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Miyamoto
H
H
Yoshioka
T
T
Katsume
A
A
Saito
H
H
Yorozu
K
K
Ueda
O
O
Itoh
N
N
Mizuguchi
H
H
Nakagawa
S
S
Ohsugi
Y
Y
Mayumi
T
T
D000464:Alginates; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002455:Cell Division; D002470:Cell Survival; D017690:Cell Transplantation; D002478:Cells, Cultured; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood*; D015850:Interleukin-6 / Q000276:immunology*; D008218:Lymphocytosis / Q000628:therapy*; D008567:Membranes, Artificial; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009929:Organ Size; D010950:Plasma Cells; D011107:Polylysine / Q000031:analogs & derivatives; D013154:Spleen / Q000473:pathology
D000464:Alginates; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015850:Interleukin-6; D008567:Membranes, Artificial; C051546:alginate-polylysine-alginate; D011107:Polylysine