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Biologics Feature

Professor Ranjeny Thomas / Courtesy of University of Queensland

“Immunotherapy” Targets Underlying Cause of RA

Elizabeth Hofheinz, M.P.H., M.Ed. • Wed, November 22nd, 2017

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Australian researchers are going right for the root cause of rheumatoid arthritis (RA) in their quest for a new treatment for the disease.

The University of Queensland (UQ) in Brisbane has just begun human trials of DEN-181, a vaccine-style treatment referred to as an “immunotherapy,” that targets the underlying cause of the disease rather than treating its inflammatory symptoms. DEN-181 is being commercialized by Dendright Pty Ltd, a start-up company of UniQuest, UQ’s commercialization company.

According to University spokespeople, “UQ’s Diamantina Institute research team, led by Professor Ranjeny Thomas, discovered the body’s immune system could be ‘re-educated’ to turn off, rather than react to a self-antigen responsible for autoimmune disease like rheumatoid arthritis. This led to the development of DEN-181.”

Professor Thomas, Dendright’s chief scientific officer, told OTW, “We were working with a mouse strain deficient in the RelB subunit of NF-kB. We found that dendritic cells purified from RelB-deficient mice and exposed to a particular antigen, could be transferred to normal recipient mice immunized to the same antigen and would suppress the immune response to this specific antigen, and not to other antigens. We then used drugs to suppress RelB expression in dendritic cells to show we could achieve the same effect.”

“Dendritic cells orchestrate the immune response to specific antigens and this can be leveraged to reprogram immune responses to specific antigens. Safety will be monitored using standard monitoring of symptoms and laboratory tests. Immunological response will be monitored by looking at the number and phenotype (effector/memory/regulatory) of antigen-specific T cells in blood, using tetramer technology.”

“There is much to learn about synovial antigens in rheumatoid arthritis, collaborations analyzing synovial tissue samples will be very fruitful. The promise of antigen-specific immunotherapy is to reduce the use of drugs with global immune suppression in rheumatoid arthritis, which would greatly enhance capacity of patients to maintain infection control in settings of relative immune compromise, such as surgery.”

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