This review summarizes the history, rationale, and latest developments in using regulatory T cells (Tregs), a rare subset of immunosuppressive T lymphocytes, as a treatment for disorders caused by unwanted immune responses, such as organ transplant rejection, graft-vs-host disease, and autoimmune diseases (e.g. type 1 diabetes).
With the approval of cell-based therapies, including the use of genetically modified cells (CRISPR/Cas9, chimeric antigen receptors) for cancer, it is time to expand this powerful paradigm to more diseases, namely those caused by immune rejection - organ transplant rejection, autoimmune attack - as well as other undesired immune responses, such as chronic inflammation and allergy. Here, we lay out the key characteristics an engineered Treg must have to be a safe and effective living drug: Specificity, Survival, Stability, and Suppression (4S).
Blood has been at the forefront of cell and gene therapy due to its accessibility and decades of work on lineage tracing (there are markers for almost every cell subset imaginable, allowing their purification by FACS) and ex vivo expansion and genetic modification (retrovirus, lentivirus, AAV, and, more recently, CRISPR/Cas9 ribonucleoprotein complexes). We're at an inflection point where we're starting to use blood cell-based treatments for non-blood diseases, such as solid tumors. The next generation of this cellular approach to medicine will see the use of immune cells to a wider range of ailments, from autoimmunity and inflammation to neurological disorders. Tregs are uniquely positioned as a special subset of cells that can be purified from blood and expanded, are antigen-specific, can be redirected to any target (TCR, CAR), induce immune suppression via several mechanisms, interacting with many cell types, and promote tissue repair.Leonardo Ferreira, PhD
Nat Rev Drug Discov 2019 10 20;18(10):749-769. Epub 2019 Sep 20.
Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
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