Ashimova, Assem2023-05-292023-05-292023Ashimova, A. (2023). Delivery of monoclonal antibodies from microencapsulated cells. School of Engineering and Digital Scienceshttp://nur.nu.edu.kz/handle/123456789/7134The use of monoclonal antibodies (mabs) is a promising therapeutic approach for the prophylaxis and treatment of a wide range of illnesses, including cancer, autoimmune, and infectious disorders. They currently rank among the most widely used drugs in the pharmaceutical sector. The area of medicine where mabs are most extensively employed is oncology. Unfortunately, the complicated and costly nature of mab design, mab secretion, and purification are prohibitive and pose a hurdle to product development and pre-clinical modification, which is a significant obstacle to the use of mab therapy in clinical practice. Additionally, parenteral mab administration also poses clinical difficulties. Patients experience mild-to-moderate injection site and infusion-related responses, despite mab therapy having a low overall reactogenicity. Here, we proposed that mabs might be efficiently given by allogeneic cells that produce mabs and are encapsulated to increase cell viability and safeguard against host immunological reactions. Various illnesses, such as diabetes mellitus, anemia, cancer, and neurodegenerative disease, have been successfully treated in animal models and people through the delivery of therapeutic drugs by microencapsulated single-cell populations. A single injection of microcapsules is anticipated to be effective since the microcapsules can be tailored to last for the duration necessary for the treatment by altering the concentration of alginate and the cross-linking of alginate with PLL. While preventing immune cells from attacking the enclosed cells, the biocompatible membrane permits a bidirectional flow of nutrients, oxygen, and waste products. When a slow, continuous mab release over a lengthy period of time is necessary, cell encapsulation-aided mab delivery is preferable to bolus mab injection. Therefore, in this pre-clinical model, we investigated the feasibility of mab administration utilizing an enclosed cell culture that expresses mab. Until now, transformed hybridoma cells have been used to produce and secrete mabs. The novelty of this study is the use of non-professional immune cells, such as murine G8 myoblasts and human HEK293 (human embryonic kidney cells) cells, to secrete mabs. These cells were transfected with plasmids that encode the heavy and light chains of human IgG specific for antigens relevant in treating cancer and COVID-19 and then enclosed in alginate microcapsules. Afterward, immunocompetent (C57/BL6J) mice were intraperitoneally implanted with the microcapsules, and changes in the level of circulating mab were evaluated. Western blotting, ELISA, and microscopy were used to characterize the mab both in vitro and ex vivo. Co-transfected G8 cells secreted intact IgG at sustained levels similar to transfected HEK293 cells. Partial characterization of the secreted mab was performed. Mice implanted with 4 microcapsules containing G8 cells secreting mab induced the detection of blood mab for 40 days. This study shows the feasibility of cell microencapsulation for the systemic delivery of intact mab. This method has potential significant therapeutic applications that call for further investigation.enAttribution-NonCommercial-ShareAlike 3.0 United StatesType of access: Embargomonoclonal antibodiesmicroencapsulated cellsPhD thesis