ABT-122: A Dual-Targeting Anti-TNF/IL-17 Therapeutic for Rheumatoid Arthritis

Rheumatoid arthritis is a severe autoimmune disorder that greatly affects the quality of life for those afflicted. Presently, there are biologic drugs that target tumor necrosis factor and other immune responses, which have shown effectiveness in treating this condition. As the search for new treatments continues, antibodies against interleukin-17 are being explored in clinical trials. Studies have shown that using antibodies against both TNF and IL-17 in a mouse model of arthritis is more effective than using either one alone.

The goal of this research was to develop a new type of dual variable domain immunoglobulin molecule capable of targeting both TNF and IL-17 for potential use in RA treatment. Using in vitro mRNA display technology, researchers identified fully human antibodies against IL-17 and improved their affinity through engineering. A series of these novel immunoglobulin molecules were created, each with different variable domains and peptide linkers.

The new molecules were evaluated through various assays, and the top candidates were studied for their pharmacokinetic properties in rats and their in vivo activity in mice. The antibodies selected had high affinity for human IL-17, which was further enhanced through molecular engineering. The best-performing molecule, ABT-122, demonstrated strong affinity, potency, and a long half-life in rats, as well as effective inhibition of human TNF and IL-17 activity in mice.

In conclusion, ABT-122 is a promising new dual-targeting immunoglobulin that shows high affinity and neutralizing potency for both TNF and IL-17. Given the positive outcomes in preclinical models and the potential of TNF-targeted therapies and IL-17 antibodies in RA, the next step will be to assess the efficacy and safety of this new DVD-Ig molecule in human clinical trials for RA.