The immunomodulatory enzyme IDO2, discovered by LIMR scientists, has been identified as an essential mediator of autoimmune disease. In preclinical models of rheumatoid arthritis (RA), systemic administration with a cell-permeable monoclonal antibody developed at LIMR that specifically binds IDO2 in B cells reduced the level of autoreactive T and B cell activation and alleviated pathogenic symptoms. LIMR’s investigators have defined a pathway that allows for effective targeting of intracellular antigens previously considered inaccessible to antibody-based therapies.
LIMR’s technology that is focused on IDO2 offers a disease-specific approach to the treatment of autoimmune disease and that is currently lacking in the field, where management is based on a general ablation of inflammatory signals or the immune system as a whole. The cell-permeable antibody developed at LIMR acts selectively within B cells to attenuate pathogenic autoantibody production without ablating normal immune function. Preclinical genetic and therapeutic proof of concept in mice has been published for this novel mechanism of action. The current stage of work is humanization of IDO2-binding antibodies with suitable properties for clinical translation.
RA is a chronic autoimmune disease that occurs when the body’s immune system attacks joints, creating debilitating inflammation and pain. Left unchecked this inflammatory condition can permanently damage joint structures, and in some cases damage the cardiovascular and respiratory systems. This systemic disease affects more than 1.5 million Americans and about one percent of the global population, with nearly three times the number of women as men. Current treatments only ease symptoms or slow disease course. They do not target the disease itself, but simply ablate the immune system generally, elevating risks of infection and other immune-based diseases such as cancer. The global market for RA therapy is expected to increase from US $1.7 billion in 2017 to US $2.3 billion in 2022, according to the market information resource BCC Research.
Intellectual property position
- IDO2 nucleic acid sequences: U.S. Patent No. 8,058,416 (issued 15 Nov 2011)
- IDO2 antibodies: U.S. Patent No. 8,436,151 (issued 7 May 2013).
Merlo LM, Pigott E, Duhadaway JB, Grabler S, Metz R, Prendergast GC and Mandik-Nayak L. (2014). IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in a mouse model of autoimmune arthritis. J Immunol 92: 2082-90.
Merlo LM, DuHadaway JB, Grabler S, Prendergast GC, Muller AJ and Mandik-Nayak L. (2016). IDO2 Modulates T cell-dependent autoimmune responses through a B cell-intrinsic mechanism. J Immunol 196: 4487-97.
Merlo LM, Grabler S, DuHadaway JB, Pigott E, Manley K, Prendergast GC, Laury-Kleintop, LD and Mandik-Nayak L. (2017). Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits autoimmune arthritis. Clin Immunol 179: 8-16.