CAR-T Meeting 2021 | CAR-Treg therapy for systemic lupus erythematosus
Regulatory T-cells (Tregs) are a subgroup of T-cells that function to maintain homeostasis and prevent autoimmunity. Matteo Doglio, MD, IRCCS Ospedale San Raffaele, Milan, Italy, discusses CAR-Treg therapy for systemic lupus erythematosus (SLE). SLE is a chronic inflammatory autoimmune disorder characterized by the production of autoantibodies B-cell derived plasma cells. The use of CARs combined with regulatory T-cells allows to boost the normal suppressive activities of lymphocytes and block the inflammatory response in autoimmune diseases. Results show that the CAR-Treg product was able to suppress the activity of normal lymphocytes in vitro. More importantly, in an in vivo model, the cells were able to slow down the disease’s progression. Dr Doglio highlights that the product needs to be improved, but the preliminary results are very encouraging. This interview took place during the 3rd European CAR T-cell Meeting.
Transcript (edited for clarity)
My work regards the development of CAR-Treg based project for systemic lupus erythematous. We decided to change a little bit the classic approach with the CARs, chimeric antigen receptors, and we decided to use them in combination with regulatory T-cells to boost the normal specific activities of regulatory T-cells. So, instead of generating cells that can kill tumor cells, we decided to use cells that block inflammatory response in autoimmune diseases...
My work regards the development of CAR-Treg based project for systemic lupus erythematous. We decided to change a little bit the classic approach with the CARs, chimeric antigen receptors, and we decided to use them in combination with regulatory T-cells to boost the normal specific activities of regulatory T-cells. So, instead of generating cells that can kill tumor cells, we decided to use cells that block inflammatory response in autoimmune diseases. We decided to use lupus because lupus is a disease in which medical treatment is suboptimal. So, a lot of patients have a chronic disease that leads to severe damages, especially in kidneys with the need of transplantation and dialysis.
So, in my work we develop these CAR-Tregs to be employed in lupus and we demonstrated that they were able to suppress the activity of normal lymphocytes, first of all in vitro, but most importantly, we evaluated our cells in vivo model humanized mouse model, so to fully recapitulate a normal immune system with a normal inflammatory response and try to replicate the model of lupus.
We injected our cells and we found that they were able to slow down the progression of the disease. We are not still able to completely cure the disease because we need to refine the model a little bit, we need to improve the product, but we have very preliminary data, but they were very encouraging … very, very encouraging.
Also, in the structure of the kidney, we found that our cells were able to slow down the disease and to maintain the normal structure of the organ.
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