Therapeutic activity of L19-IL2, rIL-2, and rituximab in mono- and combination therapies against disseminated lymphoma xenografts. SCID mice were injected IV with 2 × 106 Ramos lymphoma cells on day 0 to induce systemic disease and treated on days 8, 11, 14, and 17 (Q3D × 4) with the following regimens (≥ 6 mice per group): 6.6 μg nontargeted rIL-2 (▵), 20 μg L19-IL2 (□), 200 μg rituximab (●), 200 μg rituximab + 6.6 μg rIL-2 (▴), 200 μg rituximab + 20 μg L19-IL2 (■), or control saline (×). Data are graphed as a Kaplan-Meier survival curve of the time to terminal paralysis. The addition of L19-IL2 to rituximab was highly efficacious and inhibited clinical manifestations of disseminated lymphoma in 60% of the cases, whereas all animals treated with unconjugated rIL-2 combined with rituximab succumbed to progressive lymphoma growth (P < .001). * indicates that 1 mouse had to be killed without any symptoms of disseminated lymphoma on day 62 due to infection and was censored for Kaplan-Meier analysis; ** indicates that 2 mice developed axillary lymphoma manifestations without hind-leg paralysis, and the remaining 3 mice were still disease-free at day 310.
