Rheumatoid arthritis breakthrough the first of its kind
Professor Ranjeny Thomas with a patient.
A recent trial at Princess Alexandra Hospital and The University of Queensland saw 17 people living with rheumatoid arthritis treated with a single dose of a novel immunotherapy developed by Arthritis Queensland Chair of Rheumatology Ranjeny Thomas.
Participants between the ages of 20 and 64 received 1 of 3 different doses. Eight weeks later, all the participants in 2 of the dose groups (half of the total group) were in remission.
The trial is the first of its kind for rheumatoid arthritis in the world and will give new hope to the 456,000 Australians living with the disease. Rheumatoid arthritis occurs when the body mistakes its own proteins (self-antigens) within joint tissue as foreign, resulting in an immune response against the joint tissue.
The immunotherapy treatment was made from liposome nanoparticles that contain a peptide (collagen) antigen found in the joint tissue and an immune modulatory drug.
"No one has done a trial before of antigen-specific immune tolerance using a nanoparticle for rheumatoid arthritis," Professor Thomas said.
"This is the first one using a liposome formulation. This clinical trial provides evidence that the therapy was well tolerated, that it does modify the immune response towards the collagen antigen found in the joint tissue, and that it appears to have a broader beneficial effect on the rheumatoid immune response."
The team with a vial of the DEN-181 liposome product they developed with Janssen. Meghna Talekar, pharmaceutical scientist; Lavinia Proctor, research development consultant; Helen Roberts, CEO of Dendright; Ryan Galea, senior research technician; Hanno Nel, postdoctoral fellow; and Ranjeny Thomas.
Professor Thomas first began working on restoring immune regulation in rheumatoid arthritis in 1999.
But it wasn't easy. Between 2006 and 2012, the technology was pitched to more than 26 different entities for investment, without success, until finally a partnership was struck with pharmaceutical giant Janssen.
“When we pitched to potential investors, they advised against delivering peptide and immune modulatory drug with dendritic cells generated outside the body as it wouldn’t be translatable at large scale,” Professor Thomas said.
“Based on this feedback we set out to develop a new format of the drug, with the inhibitor and peptide encapsulated in a liposome particle that could be injected directly and would be taken up by the immune cells in the lymph nodes of patient.”
A liposome nanoparticle is a small package about a hundred times smaller than a cell, similar to what is used to deliver mRNA vaccines.
It was with Janssen that Professor Thomas and her colleagues developed the potential treatment in the format of an immunotherapy and were able to run trials in humans between 2017 and 2019.
A low dose of the product when combined with methotrexate was beneficial in rheumatoid arthritis patients, potentially through 'bystander regulation', where regulation of the immune system towards one peptide broadens and leads to a deeper immune reset.
Bystander regulation has not been demonstrated in trials before. To be able demonstrate this, the team developed specialised tests for the immune cells in blood.
“Everybody in the two lowest dose groups ended up in remission within 8 weeks. Although this is a first in human trial with only a small number of patients in each group, it’s a really positive sign that we could show the impact of dose on symptoms and how that related to the immune response.
“What we could show is that we got a response to the antigen we included, as well as a bystander response to another rheumatoid-related citrullinated antigen.
Pharmaceutical scientist Meghna Talekar in the lab.
“Very interestingly, the antibodies also changed. That really is one of the tantalising and very exciting parts of this trial, because normally those antibodies don’t change in response to our current therapies.”
Professor Thomas hopes this trial will provide a boost to further trials of antigen-specific immunotherapy in rheumatoid arthritis and other autoimmune diseases.
"While a product for treatment of rheumatoid arthritis is still years away, this trial of antigen-specific immunotherapy now opens the door to exciting trials to look at potential for long-term disease control and prevention in people at risk" she said.
They are keen to hear from parents, siblings and adult children of people living with rheumatoid arthritis to participate in research.
For more information, please contact the team at di.arthritis@uq.edu.au.
The application of this antigen specific immunotherapy technology as a treatment for rheumatoid arthritis and certain other autoimmune diseases is available for partnering or investment from UniQuest.
Professor Ranjeny Thomas is focused on the study of the biology and clinical use of human dendritic cells in autoimmune disease. She has explored basic mechanisms of immunity and dendritic cell function in autoimmune disease.
Contact:
ranjeny.thomas@uq.edu.au
+61 7 344 36960