FIG. 5.

Dose splitting impacts efficacy of mRNA CAR T cells. (A) This is a composite survival of 4 independent experiments (with 3 different donors, n=20) using 10⁶ Nalm-6 on day 0 and either a single dose 2.5×10⁷ on day 7, or split infusions on days 7, 14, and 28 with interval CTX at 60 mg/kg IP×1 24 hr before CTL doses 2 and 3. Survival is significantly improved by the 20–5–5 schedule despite the total dose of T cells being equivalent (p=0.00103). The only long-term survivors are observed with this dose schedule. (B) Compressed T-cell infusion schedule further improves efficacy. This composite of 2 experiments with 2 donors demonstrates the significant effect of a compressed infusion schedule of 20–5–5 on days 7–14–21 (n=15, p<0.0001). The compressed infusion and CTX schedule did result in some meso–41BBz-treated mice surviving beyond CTX-only controls, perhaps reflecting a slight allogeneic effect of this donor against Nalm-6 (see Supplementary Fig. S2 for further investigation). The difference approached significance for control versus meso–41BBz (p=0.09), while the comparison of control versus anti-CD19-targeted RNA CAR T cells from the same donor was highly significant (p<0.001).