Combination of the Pro-Apoptotic TRAIL-Receptor Antibody Mapatumumab With Ionizing Radiation Strongly Increases Long-Term Tumor Control Under Ambient and Hypoxic Conditions
- Department of Radiation Oncology, CCC Tuebingen, University of Tuebingen, Tuebingen (Germany)
- Department of Radiation Oncology and Radiotherapy, University of Duesseldorf, Duesseldorf (Germany)
- Department of Cell Biology (Cancer Research), University of Essen, Essen (Germany)
Purpose: Mapatumumab, an agonistic tumor necrosis factor-related apoptosis inducing ligand-receptor antibody, exerts highly synergistic apoptotic effects in vitro and in short-term growth delay assays when combined with irradiation. Because it remained unclear in how far these effects influence local tumor control, long-term experiments using a colorectal xenograft model were undertaken. Material and Methods: Experiments were performed with irradiation (5 x 3 Gy, d1-5) and mapatumumab (10 mg/kg) in Colo205-xenograft-bearing NMRI (nu/nu) nude mice. Graded top up doses were delivered on the tumor-bearing hind leg under ambient and hypoxic conditions; follow-up was 270 days. Growth delay and local tumor control were end points of the study. Statistical analysis of the experiments included calculation of tumor regrowth and local tumor control. Results: After combined treatment, a pronounced tumor regrowth-delay was observed when compared with irradiation alone. Long-term experiments revealed a highly significant increase in local tumor control for ambient (p = 0.00076) and hypoxic treatment (p = 0.000069). Conclusions: The present data demonstrate for the first time that combination of a pro-apoptotic antibody with irradiation results in evidently reduced tumor regrowth times and subsequently highly increased local tumor control under normoxic and hypoxic conditions in a xenograft mouse model.
- OSTI ID:
- 21282014
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 75, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2009.04.038; PII: S0360-3016(09)00612-9; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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