Heading in a new direction – Novel CARs specific for CD25 to treat chronic inflammatory processes
- Chimeric antigen receptors to target chronic inflammation
- Therapeutic effect independent of tissue type and source
- Applicable to any inflammatory process
The last years have revolutionized cancer treatment with novel approaches using the patients’own immune cells. CAR T cell therapy is furthest in clinical development and showed remarkablesuccess in treating leukemia and advanced lymphomas1. Chimeric antigen receptors (CARs) arerecombinant and modular trans-membrane receptors directed against different antigens and ex-pressed on the surface of T cells via gene transfer. The genetically modified T cells are expanded exvivo to then be re-infused back to the patient to act as a “living drug”. By binding to their targetedantigen, CAR T cells become cytotoxic and destroy the bound tumor cells. Knowledge on CAR Tcells is now implemented into areas beyond cancer. In this context, chronic inflammation has comeinto focus. Common treatment options comprise the less effective nonsteroidal anti-inflammatorydrugs and immunosuppressive steroids that act systemically and are associated with severe sideeffects. Specifically in autoimmune settings (e.g. in multiple sclerosis and rheumatoid arthritis) withthe body’s immune system attacking its own tissues, the physiological function of regulatory T cells(Treg cells) to inhibit persistent inflammatory reactions, is not effective. There is a great need formore targeted therapeutics.
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Our innovation applies the CAR T-cell technology in the context of chronic inflammatory processes.Here, CARs with specificity for CD25 (IL-2 receptor) were generated and, via gene transfer, expres-sed on cytotoxic T cells and suppressive Treg cells. Upon contact with activated immune cells, an-ti-CD25 T cells are able to diminish pro-inflammatory immune reactions by limiting tumor cell lysisand pro-inflammatory IL2-secretion independent of the tissue type. This approach can be used tocontrol the persistent and de-regulated inflammatory response in autoimmune settings.
- High CD25-specificity for targeted suppression
- Anti-inflammatory effect is independent of tissue type
- Opportunities for partners include e.g. collaboration for in vivo studies