Regulatory T Cell Therapies Advance for Autoimmune Diseases and Transplant Rejection
Engineered regulatory T cell therapies are progressing through clinical trials for autoimmune diseases and organ transplant rejection, with CAR-Treg candidates showing promising early results in rheumatoid arthritis and other conditions.
Regulatory T cell therapies are emerging as a promising approach for treating autoimmune diseases and preventing organ transplant rejection, with multiple candidates advancing through clinical development. These specialized immune cells, known as Tregs, function as the immune system's peacekeepers by suppressing inappropriate immune responses.
Sonoma Biotherapeutics in California has developed SBT-77-7101, a chimeric antigen receptor (CAR) Treg therapy designed to treat autoimmune conditions such as rheumatoid arthritis and hidradenitis suppurativa, a chronic skin disease. The candidate targets disease-causing proteins in the inflamed areas to dampen inflammation. In phase 1 trials, the therapy demonstrated deeper reductions in joint counts in patients who received a higher dosage versus the lower dosage cohort. Around 67% of patients saw swelling decline by half and 83% had a depletion of the harmful proteins. The drug was found to be safe, according to the trial.
The therapy works without the need for conditioning chemotherapy, supporting the approach pioneered by Sonoma as it works to develop a new generation of targeted and durable Treg cell therapies. When the immune system attacks the joints in rheumatoid arthritis, it causes painful swelling and stiffness around the joints.
Coya Therapeutics in Texas has received IND approval for COYA 301, a Treg-enhancing therapy administered through the skin. The candidate is made up of two signaling molecules, low dose IL-2 and CTLA-4 Ig, and heightens the anti-inflammatory properties of Treg cells so that they can suppress inflammation that is activated by immune cells.
Kincell Bio and RegCell announced a collaboration to advance regulatory T cell therapies. Under the agreement, Kincell will support RegCell's lead Treg program by providing CMC development, process and analytical transfer, scalable manufacturing process optimization, and GMP clinical material supply to facilitate IND-enabling activities and clinical trials. RegCell's platform converts CD4+ T cells into stable, antigen-matched Tregs by replicating key epigenetic features involved in Treg stability. The platform does not rely on gene editing or viral DNA reagents, which reduces manufacturing complexity and allows for potential automation and point-of-care applications.
Cellular immunotherapies encompass a broad and rapidly developing group of treatments comprising expanded and/or genetically engineered immune cells, which use the specific properties of human immune cells to counteract human immune-mediated disease. Initially approved for cancers of the B cell lineage, a growing arsenal of cellular immunotherapies are being applied to autoimmune diseases, including chimeric antigen receptor (CAR) T cells, chimeric autoantibody receptor T cells, regulatory T cells and CAR-engineered innate immune cells.
Regulatory T cells were discovered more than three decades ago. Without Tregs, the immune system might react excessively, which could cause the body to attack its own cells. This may lead to autoimmune disease. A mutation in the gene Foxp3 was found that was linked to the development of an autoimmune condition called autoimmune polyendocrine syndromes that causes early-onset autoimmunity in children. The Foxp3 gene controls the Treg cells, linking their dysfunction to the development of autoimmune diseases.
In organ transplantation, nanotechnology-driven approaches are being explored to enable spatiotemporally precise immune modulation. Organ transplantation represents a definitive therapeutic modality for end-stage organ failure, yet it is plagued by formidable challenges encompassing allogeneic immune rejection and the inherent limitations of conventional immunosuppressive regimens. Nonspecific immunosuppression not only precipitates severe adverse events such as opportunistic infections and malignancies but also fails to precisely modulate the local immune microenvironment. Long-term recipient survival is still limited by allogeneic immune rejection. Existing immunosuppressants significantly reduce the risk of acute rejection, however their non-specific immunosuppressive properties can cause severe side effects, including opportunistic infections, malignancies, and metabolic disorders.