A CD8α hinge-based CAR targeting CD22 was found to outperform a CD28 hinge-based CAR in vitro against low antigen density leukemia, and it was suggested that the flexibility of the CD8α hinge, driven by cis-trans isomerization, in combination with disulfide bridging between dimeric molecules, enhanced the signal transmission and sensitivity of the CAR (72). Here, CD8A is linked to leukemia.