In this study, we demonstrated the toxic activity of a novel agonistic anti-DR4 Fab in TRAIL-resistant and mildly TRAIL-resistant cells, including leukemia and lymphoma cell lines (Jurkat, THP-1, Molt-4, and U937), as well as TRAIL-sensitive leukemia cells (HL60), but not in normal human cells. The gene discussed is TNFSF10; the disease is lymphoma.