Combination of the pro-apoptotic TRAIL-receptor antibody mapatumumab with ionizing radiation strongly increases long-term tumor control under ambient and hypoxic conditions.

摘要: Purpose Mapatumumab, an agonistic tumor necrosis factor–related apoptosis inducing ligand-receptor antibody, exerts highly synergistic apoptotic effects in vitro and short-term growth delay assays when combined with irradiation. Because it remained unclear how far these influence local control, long-term experiments using a colorectal xenograft model were undertaken. Material Methods Experiments performed irradiation (5 × 3 Gy, d1–5) mapatumumab (10 mg/kg) Colo205-xenograft–bearing NMRI (nu/nu) nude mice. Graded top up doses delivered on the tumor-bearing hind leg under ambient hypoxic conditions; follow-up was 270 days. Growth control end points of study. Statistical analysis included calculation regrowth control. Results After treatment, pronounced regrowth-delay observed compared alone. Long-term revealed significant increase for ( p = 0.00076) treatment 0.000069). Conclusions The present data demonstrate first time that combination pro-apoptotic antibody results evidently reduced times subsequently increased normoxic conditions mouse model.