Abstract
The clinical application of immune effector cells genetically modified to express chimeric antigen receptors (CARs) has shown impressive results including complete remissions of certain malignant hematological diseases. However, their application can also cause severe side effects such as cytokine release syndrome (CRS) or tumor lysis syndrome (TLS). One limitation of currently applied CAR T cells is their lack of regulation. Especially, an emergency shutdown of CAR T cells in case of life-threatening side effects is missing. Moreover, targeting of tumor-associated antigens (TAAs) that are not only expressed on tumor cells but also on vital tissues requires the possibility of a switch allowing to repeatedly turn the activity of CAR T cells on and off. Here we summarize the development of a modular CAR variant termed universal CAR (UniCAR) system that promises to overcome these limitations of conventional CARs.
Highlights
After almost 3 decades of development, in which renowned scientists around the world were involved, T cells genetically modified to express artificial receptors have arrived in the clinic1 3 Vol.:(0123456789)Cancer Immunology, Immunotherapy (2019) 68:1713–1719[for reviews, e.g., 1–3]
chimeric antigen receptors (CARs) consist of an extracellular target recognition domain, a transmembrane domain (TMD) and intracellular signaling domain(s) [e.g., 9–11, see Fig. 1]
The extracellular domain of a CAR is commonly constructed from the variable domains of the heavy and light chains of a monoclonal antibody in a single-chain fragment variable format
Summary
After almost 3 decades of development, in which renowned scientists around the world were involved, T cells genetically modified to express artificial receptors (termed as chimeric antigen receptors, CARs) have arrived in the clinic1 3 Vol.:(0123456789)Cancer Immunology, Immunotherapy (2019) 68:1713–1719[for reviews, e.g., 1–3]. On-target/ off-tumor effects can even occur during an anti-CD19 CAR T-cell therapy as CD19 is expressed on the surface of healthy B cells.
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