Figure 6.
High-dose CD22sdCAR treatment leads to complete tumor responses
CAR-T cells were generated from healthy donor PBMCs as described in the Materials and methods section and prepared for injection on day 14 after transduction. NSG mice were injected with 5 × 104 Ramos-FLUC cells and randomly assigned to cages. At day 3, cage groups were treated with 2.5 × 106 (marginal dose) or 12.5 × 106 (high dose) CD22 CAR-T cells or equivalent to the highest total dose of unmodified (mock) T cells (n = 5 mice per group). Mice were assessed for tumor engraftment via IVIS imaging for bioluminescent signal from Ramos-FLUC tumors at various time points as shown in (A) bioluminescent signal data per mouse over the timecourse and in (B) mouse images. (C) Blood samples were also obtained at regular intervals for the assessment of hCD45+hCD19−NeonGreen+ CAR-T cells via flow cytometry. (D) Surviving mice in the high-dose treatment group were rechallenged with an additional dose of 5 × 104 Ramos-FLUC cells intravenously, including new untreated control mice with no cell treatment. Graphs show the bioluminescent signals for 1ug36, m971, or untreated mice. (E) Proportion of surviving mice at various time points throughout the experiment is shown. p values show intertreatment group comparison at similar dose levels via the log-rank test.