Bister A, Ibach T, Haist C, et al. Optimized NGFR-Derived Hinges for Rapid and Efficient Enrichment and Detection of CAR T Cells in vitro and in vivo. Molecular Therapy — Oncolytics. 2022; 26: 120 (doi: 10.1016/j.omto.2022.05.012).
The next generation of chimeric antigen receptor (CAR) constructs might be assembled with novel hinge domains derived from human nerve growth factor receptor (NGFR). Hinges, the mechanism for bringing together the extracellular antigen recognition unit and the transmembrane domain, provide the structure that makes it possible for the CAR to get to the target antigen and commence with recognition and killing of target cells. Working the two new NGFR-based hinges, known as N3 and N4, into the CAR backbone promotes fast detection and high-grade enrichment of CAR T cells. Researchers showed that N3- and N4-hinged CAR T cells have an effect against hematological blasts in vitro that is on par with CD8-hinged CAR T cells. From an in vivo perspective, the novel hinges are equally powerful as CD8-hinged counterparts in controlling acute monocytic leukemia in an immunodeficient murine xenograft model.