FIG. 2.
Interval lymphodepletion produces a sustained antitumor effect with multiple infusions of mRNA CAR T cells. (A) CTX plus mRNA CAR T cells produce a more sustained disease control than that without CTX. NSG mice bearing Nalm-6 CBG were treated with 107 mRNA CAR T cells on days 7, 14, and 28 with 60 mg/kg CTX IP 24 hr before injections 2 and 3. While disease responded to the first injection of anti-CD19 CAR T cells, only with CTX did subsequent infusions have any impact on disease progression. About 107 stably transduced CAR T cells (via lentiviral vector) produce a sustained disease response as well, and this is not lost with CTX treatment. mRNA CAR T cells directed against mesothelin with CTX do not affect disease progression. (B) The reduction in disease burden correlates with increased median survival (n=5 per arm).