Efficient in vivo activity exerted by CD20xCD22 CAR T cells against different combinations of antigen-expressing cells in an aggressive lymphoma model. A, Schematic showing tumor model experimental design with NSG mice injected subcutaneously with Raji cells (Burkitt lymphoma). B, Kaplan–Meier curves showing survival of NSG animals with subcutaneous Raji tumors treated with different versions of CD20xCD22 CAR and CD22 CAR T cells (n = 3–6). C, BLI of tumors of NSG mice treated with indicated CAR T cells and measured at different timepoints. D, Graphs measuring of growth of CD20+CD22+, CD20+CD22−, and CD20−CD22+ tumors, respectively, after treated with the indicated does of CD22.CD20CAR, CD20.CD22CAR, and CD22CAR as indicated. Average radiance (photons/second/cm2/sr) is shown. E, Schematics showing the design of the disseminated lymphoma model study with different Raji cells to model antigen escape. F and G, Tumor growth control overtime and Kaplan–Meier curves after intravenous administration of Raji tumor cells and CAR T-cell treatment with the indicated constructs (n = 5). Statistical value was calculated against vehicle. Log-rank Mantel–Cox test was calculated for survival curves. Significant values are indicated. P-value definition: *<0.05, **<0.01, ***<0.001, ****<0.0001. WT, wild-type.