Fig. 4.

αCD20 MATCH in vivo efficacy against a human non-Hodgkin’s lymphoma xenograft in C.B-17 SCID mice. (A) Dosing regimen. A co-culture of luciferase-expressing Raji cells (4 × 105) and healthy donor, naïve T-cells (2 × 106) was inoculated via tail vein into female C.B-17 SCID mice. Cells were allowed to disseminate for 1 h before dosing began. Consecutive αCD20 MATCH was administered via tail vein in two consecutive injections 5 h apart. The first injection contained the B-cell engager, Fab′CD20-MORF1 (60 μg; 100 μL). The second injection contained the T-cell engager, Fab′CD3-MORF2, at serial dilutions for each cohort: 60 μg, 20 μg, 6 μg, or 2 μg. Consecutively dosed mice were also compared to a premixed αCD20 MATCH cohort who received a single MATCH injection containing the B-cell engager and the T-cell engager pre-hybridized (60 μg; 100 μL). Blinatumomab (αCD3/CD19) was administered as a single bolus tail vein injection (60 μg; 100 μL) as the clinical standard control treatment. (B) Paralysis-free survival curves plotting mouse survival up to 150 days post-inoculation. (C) Tissue analysis for residual disease in long-term surviving mice. Mechanically sieved cell suspensions were processed and analyzed for residual human B-cell presence via flow cytometry (FACSCanto). (D) Mice were monitored biweekly via bioluminescence detection using IVIS optical imaging. Sample images depicted were taken 21 days post-inoculation (additional images can be found in Supplementary Fig. S14). Images are adjusted to the luminescence scale depicted on the right in Radiance (p sec−1 cm2 −1 sr−1). Cohorts of mice (n = 7 per group) were randomly distributed (α = 0.05, power = 0.80); significance determined by logrank (Mantel-Cox) test. **p < 0.01, *p < 0.05, n.s. not significant by One-Way ANOVA and Tukey test.