In terms of CRS, there is a higher incidence at grades 1 and 2 with CARs using the CD28 hinge and transmembrane domains (73% versus 39% for CARs using other architectures), though there is insufficient data to determine if this differs based on the costimulatory domain used, given that only 10 patients in a single trial received a FMC63-CD28-CD28-41BB-3ζ CAR, versus 501 patients with published data who received FMC63-CD28-CD28-CD28-3ζ CAR. Here, CD28 is linked to congenital rubella syndrome.