Figure 5.
Effect of CD38-bispecific PRIT on tumor growth rate and survival of mice bearing H929 (MM) xenografts. Athymic nude mice (n = 10 per group) with H929 xenografts were injected at −24 hours with a pretargeting protein (CD38 bispecific or control [anti-CD20] bispecific), then at −1 hour with CA, and at 0 hours with 1200 µCi 90Y-DOTA–biotin. Tumor volume was monitored 3 times weekly and mice were euthanized when tumor size reached IACUC-mandated limits. For tumor volume graphics, data from euthanized mice were retained until all mice in a group died. (A) Treatment with CD38-bispecific PRIT (red) resulted in 100% CRs during days 15 to 30 and 80% long-term complete remissions. This contrasted with control mice, where 90% of untreated (black) and 100% of control bispecific groups (gray) died of tumor progression by day 27 (P ≤ .0001, CD38 bispecific vs either control group, error bars = 1 SEM). One untreated mouse exhibited spontaneous tumor remission. (B) Kaplan-Meier analysis indicates that CD38-bispecific PRIT significantly improved survival over controls (P ≤ .0001), curing 80% of mice. Cure was defined as no sign of tumor recurrence at day 150.