Novel CD19 and CD20 scFvs were selected for enhanced CAR performance and combined with the existing CD22 scFv used in firi-cel. These new binders are fully human to limit host-mediated rejection. The iterative engineering allowed for the selection of the optimal costimulatory domain configuration and optimal assemblage in the lentiviral vector used https://www.sciencedirect.com/science/article/pii/S0006497124047827