Solving Autoimmunity: Destroy The Troublemakers

Posted on 1 July 2016

Magnification of a sample from a patient with pemphigus vulgaris

Magnification of a sample from a patient with pemphigus vulgaris

In a groundbreaking development in the field of autoimmunity, researchers have discovered a way to specifically target and remove a subset of immune cells responsible for the autoimmune disease pemphigus vulgaris

Pemphigus vulgaris is a deadly in which a patient’s own immune cells attack the adhesive proteins binding skin cells together – more specifically a protein called desmoglein-3 (Dsg3). It falls within a group of autoimmune disease including rheumatoid arthritis, which doctors struggle to control. Today we have immune suppressing medicines at our disposal like prednisone and rituximab, but these leave patients more vulnerable to infection and even cancer. We sorely need better solutions. 

A game changer

Researchers at the University of Pennsylvania have developed a novel strategy, taking a leaf from immunotherapy’s book in the fight against cancer; engineering custom T-cells to attack a subset of the immune system. 

“This is a powerful strategy for targeting just autoimmune cells and sparing the good immune cells that protect us from infection. Our study effectively opens up the application of this anti-cancer technology to the treatment of a much wider range of diseases, including autoimmunity and transplant rejection”

CAR T-cells

Credit: Memorial Sloan Kettering Cancer Center

Credit: Memorial Sloan Kettering Cancer Center

CAR stands for chimeric antigen receptor, and in particular immunotherapy approaches T type immune cells are removed from a patient and modified to produce this new receptor. This new CAR receptor is specific to a protein produced by whichever target you have in mind. You have to make sure this protein is primarily present on your target however, and not in a large amount of other cells – or you’ll kickstart an even more catastrophic autoimmune attack. Immunotherapy is essentially fighting fire with fire, and it can be extremely dangerous in certain cases. Your immune system is not something you want as an enemy. 

These strategies have been extremely successful in recent cancer trials, and researchers began to wonder whether they could use a similar approach to target the B-cells responsible for autoimmunity. Pemphigus vulgaris, like many other conditions, is driven by a portion of B-cells that produce antibodies to one of the body’s own molecules. 

“We thought we could adapt this technology that’s really good at killing all B cells in the body to target specifically the B cells that make antibodies that cause autoimmune disease. Targeting just the cells that cause autoimmunity has been the ultimate goal for therapy in this field”

Desmoglein-3 is one of the proteins responsible for binding skin cells together effectively 

Desmoglein-3 is one of the proteins responsible for binding skin cells together effectively 

This is exactly what they did

The University of Pennsylvania team developed a chimeric autoantibody receptor (CAAR) that contained fragments of desmoglein-3 – the protein targeted by these B-cells. When these new T-cells were injected back into a mouse model, they effectively attracted these troublesome B-cells; drawing them into contact and enabling the T-cells to take them out. Despite being bombared with antibodies from the B-cells, the hardy T-cells were still able to survive and effectively remove these cells. 

“We were able to show that the treatment killed all the Dsg3-specific B cells, a proof of concept that this approach works. If you can identify a specific marker of a B cell that you want to target, then in principle this strategy can work”

This study is great news for autoimmunity. If the method can be perfected and tested for safety initially on animals, it would very well prove to be a game changer for those suffering with autoimmune conditions. 

Read more at MedicalXpress

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