Book Description
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and progressive joint destruction. Anti-TNF biologics have been developed to treat RA and although effective in the majority of patients, they require repeated administration and systemically inhibit TNF. This systemic inhibition leads to systemic immune suppression and can result in side-effects including opportunistic infections, serious infections and malignancy. To address these limitations, I developed a novel, local-acting biologic known as TNF sticky trap. This biologic was shown capable of inhibiting TNF while sticking or localizing to the extracellular matrix (ECM) where it is produced or administered. Next, cell lines inducibly expressing this local-acting biologic were generated, characterized and evaluated for their therapeutic efficacy in an animal model of RA. A single injection of cells expressing TNF sticky trap was sufficient to reduce arthritis and this local-acting biologic was undetectable in the serum of treated animals. Lastly, to help advance the translation of RA cell therapies into the clinic, a cell safety mechanism was developed and characterized. The development of a safe cell therapy inducibly expressing local-acting biologics could avoid the limitations associated with systemic therapies and improve the current treatment of RA.
