[Genetically modified regulatory T cells: therapeutic concepts and regulatory aspects]

Adoptive T‑cell therapies are emerging tools to combat various human diseases. CAR‑T cells are approved and marketed as last line therapeutics in advanced B‑cell lymphomas and leukemias. TCR-engineered T cells are being evaluated in clinical trials for a variety of hematological and solid tumors. Genetically modified regulatory T cells, however, are still in the initial stages of clinical development for the induction of immune tolerance in various indications.Here we outline the general role of regulatory T cells in establishing self-tolerance and the mechanisms by which these suppress the effector immune cells. Further, the role of regulatory T cells in the pathomechanism of certain immune diseases is presented, and the current status of clinical developments of genetically modified Treg cells is discussed. We also present the regulatory framework for genetically modified regulatory T cells as advanced therapy medicinal products, including aspects of manufacture and quality control, as well as nonclinical and clinical development requirements.