Host cell in vivo production of the synthetic drug anti–CD25/IL‐10 using minicircle vector

Abstract

Synthetic biologic drugs are highly successful for induction therapy in transplantation, but the development of novel biologics is limited because of the high cost of synthesis and purification. In this study, we developed a novel strategy for the production of synthetic protein drugs in vivo by the host itself. We utilized minicircle (MC) technology, which can robustly express a target molecule and secrete it from cells, as an indirect method to produce a protein of interest in vivo. We designed an MC vector containing the sequences of basiliximab (anti‐CD25 mAb) and IL‐10. We verified the substantial production of the anti—CD25/IL‐10 protein from the MC in vitro and in vivo. The therapeutic effect of MC‐derived anti—CD25/IL‐10 was evaluated in a skin allograft mouse model by single intravenous infusion. Mice treated with the MC encoding anti—CD25/IL‐10 exhibited prolonged skin allograft survival times accompanied by improved histologic changes and immunologic regulation. These findings indicate that the anti—CD25/IL‐10 protein drug obtained by MC technology is functionally active and relevant for reducing allograft rejection. This self‐reproducible strategy for synthetic protein drugs using MCs is a promising tool for transplantation.—Lim, S. W., Shin, Y. J., Luo, K., Quan, Y., Ko, E. J., Chung, B. H., Yang, C. W. Host cell in vivo production of the synthetic drug anti‐CD25/IL‐10 using minicircle vector. FASEB J. 33, 10889–10901 (2019). http://www.fasebj.org

Therapeutic effect of multiple functional minicircle vector encoding anti-CD25/IL-10/CXCR3 in allograft rejection model

“…Because the blocking of CD25 and the production of IL-10 in T cells play important roles in preventing allograft rejection, we previously designed a DTA [ 31 ]. In this study, we designed the MTA as the CXCR3 sequence conjugated to the anti-CD25 antibody and IL-10 sequence by linkers ( Supplementary Tables 1 and 2 ).…”

“…We have previously suggested a platform system to promote the self-production of therapeutic protein drugs by the host itself [ 31 ]. In this study, we evaluated a new synthetic protein drug (anti-CD25 mAb, IL-10, and CXCR3) in the form of an antibody-cytokine fusion using this system.…”