Figure 6.
Comparative effects of CD38-bispecific PRIT and CD38-SA PRIT on tumor growth and survival of mice bearing Namalwa (CD38+BL) xenografts. Athymic nude mice (n = 8 per group) with Namalwa xenografts were injected at −24 hours with a pretargeting protein (CD38 bispecific, CD38-SA, or control [anti-CD20] bispecific), then at −1 hour with CA, and at 0 hours with 1200 µCi 90Y-DOTA–biotin. Tumor volumes were monitored 3 times weekly and mice were euthanized when tumor size reached IACUC-mandated limits. For tumor volume graphics, data for euthanized mice were retained until all mice in a group died. (A) CD38-bispecific PRIT (red) and CD38-SA PRIT (blue) each reduced tumor volumes to undetectable levels by day 21, followed by a single tumor recurrence in the CD38-SA group and no recurrences in the CD38-bispecific group (P < .0001, either CD38 PRIT group vs either control group, error bars = 1 SEM). (B) Kaplan-Meier survival analysis. CD38-bispecific PRIT cured 75% of mice (all mortality due to early weight loss), whereas CD38-SA PRIT cured 88% of mice (all mortality due to tumor progression), demonstrating that at this 1200-µCi dose, the 2 CD38 treatments each benefitted survival with high and equivalent efficacy (P < .0001 for either CD38 treatment vs either control, P = .48 for CD38 bispecific vs CD38-SA). Cure was defined as the absence of tumor recurrence through day 150.