Self in vivo production of a synthetic biological drug CTLA4Ig using a minicircle vector.
Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA4Ig, abatacept) is a B7/CD28 costimulation inhibitor that can ward off the immune response by preventing the activation of naïve T cells. This therapeutic agent is administered to patients with autoimmune diseases such as rheumatoid arthritis. Its antiarthritic efficacy is satisfactory, but the limitations are the necessity for frequent injection and high cost. Minicircles can robustly express the target molecule and excrete it outside the cell as an indirect method to produce the protein of interest in vivo. We inserted the sequence of abatacept into the minicircle vector, and by successful in vivo injection the host was able to produce the synthetic protein drug. Intravenous infusion of the minicircle induced spontaneous production of CTLA4Ig in mice with collagen-induced arthritis. Self-produced CTLA4Ig significantly decreased the symptoms of arthritis. Injection of minicircle CTLA4Ig regulated Foxp3(+) T cells and Th17 cells. Parental and mock vectors did not ameliorate arthritis or modify the T cell population. We have developed a new concept of spontaneous protein drug delivery using a minicircle vector. Self in vivo production of a synthetic protein drug may be useful when biological drugs cannot be injected because of manufacturing or practical problems.
CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, South Korea.
Yeri Alice
YA
Rim
CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, South Korea.
Hyoju
H
Yi
CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, South Korea.
Youngkyun
Y
Kim
CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, South Korea.
Narae
N
Park
CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, South Korea.
Hyerin
H
Jung
CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, South Korea.
Juryun
J
Kim
1] CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, South Korea [2] Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, Republic of Korea.
Seung Min
SM
Jung
Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, Republic of Korea.
Sung-Hwan
SH
Park
1] CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, South Korea [2] Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul. 137-701, Republic of Korea.
Ji Hyeon
JH
Ju
D000069594:Abatacept; D000818:Animals; D018501:Antirheumatic Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004270:DNA, Circular / Q000008:administration & dosage / Q000096:biosynthesis*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage / Q000096:biosynthesis*; D018796:Immunoconjugates / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D058990:Molecular Targeted Therapy; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D018501:Antirheumatic Agents; D004270:DNA, Circular; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept