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Apr 15 2025
6Scientists have developed a groundbreaking approach to immunotherapy by engineering T cells not to kill, but to protect. These synthetic suppressor T cells offer a targeted method of immunosuppression, which could revolutionize treatments for autoimmune disorders and transplant rejection—conditions that currently depend on generalized immune suppression, leaving patients vulnerable to infections and cancer.
Maintaining immune balance is a delicate task. A weak immune system fails to defend against pathogens and malignancies, while an overactive one can cause autoimmune diseases or reject transplanted organs. Traditional chimeric antigen receptor (CAR) T cell therapies have proven highly effective in targeting cancer, but they can also mistakenly attack healthy tissue. Meanwhile, current treatments for overactive immune conditions rely on systemic drugs that weaken the entire immune system.
To address these limitations, researchers led by Wendell Lim at the University of California, San Francisco, engineered a new class of CD4+ T cells that exert localized immunosuppressive effects. Inspired by the body's natural regulatory T cells, which control inflammation, the team created synthetic cells capable of detecting specific surface antigens and responding by dampening immune activity at the site of inflammation.
These customized cells use synthetic Notch (synNotch) receptors—a versatile platform designed to recognize chosen antigens. When triggered, the cells release anti-inflammatory compounds and soak up inflammatory cytokines. In a recent Science publication, Lim’s team demonstrated that these suppressor cells can be tailored to deliver various immune modulators only in the presence of target antigens.
The researchers tested these cells against CAR T cells in vitro, using the antigen CD19, commonly associated with B cell cancers and autoimmune conditions. The engineered suppressor T cells released molecules such as interleukin-10, programmed death ligand 1, transforming growth factor-β1 (TGFβ1), and CD25, which absorbed inflammatory interleukin-2. Among the configurations tested, cells that combined TGFβ1 and CD25 in a single-cell format were the most effective at reducing CAR T cell proliferation and protecting target leukemia cells.
To explore their functionality in living systems, the team conducted a mouse model study involving two tumors per mouse. One tumor expressed Her2, a protein recognized by CAR T cells, and the other expressed both Her2 and CD19. The suppressor T cells protected the dual-antigen tumor while allowing CAR T cells to destroy the Her2-only tumor—proving the ability of synthetic suppressors to provide precise, local immune regulation.
In another experiment involving pancreatic islet transplantation, researchers introduced insulin-producing beta cells engineered to express CD19. Mice that received both CAR T cells and synthetic suppressors retained functional beta cell grafts, while those given only CAR T cells lost the transplants. Imaging revealed that the suppressor cells physically surrounded the CAR T cells, preventing them from clustering and initiating cell destruction. Glucose testing confirmed the success of the transplant, as mice showed active insulin production.
This strategy may offer new hope in preventing transplant rejection and treating autoimmune conditions like multiple sclerosis. Lim and his team aim to expand the technology’s applications and investigate its compatibility with other immune components, including B cells and antibodies.
“This platform is incredibly versatile and opens up a range of therapeutic possibilities,” said Lim.
Source: https://www.the-scientist.com/synthetic-t-cells-provide-precision-immunosuppression-72699
This is non-financial/medical advice and made using AI so could be wrong
