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Radiation Oncology
Published in: Radiation Oncology 1/2009

Open Access 01-12-2009 | Research

Combined treatment with lexatumumab and irradiation leads to strongly increased long term tumour control under normoxic and hypoxic conditions

Authors: Patrizia Marini, Dorothea Junginger, Stefan Stickl, Wilfried Budach, Maximilian Niyazi, Claus Belka

Published in: Radiation Oncology | Issue 1/2009

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Abstract

Purpose

The combination of ionizing radiation with the pro-apoptotic TRAIL receptor antibody lexatumumab has been shown to exert considerable synergistic apoptotic effects in vitro and in short term growth delay assays. To clarify the relevance of these effects on local tumour control long-term experiments using a colorectal xenograft model were conducted.

Materials and methods

Colo205-xenograft bearing NMRI (nu/nu) nude mice were treated with fractionated irradiation (5× 3 Gy, d1-5) and lexatumumab (0.75 mg/kg, d1, 4 and 8). The tumour bearing hind limbs were irradiated with graded single top up doses at d8 under normoxic (ambient) and acute hypoxic (clamped) conditions. Experimental animals were observed for 270 days. Growth delay and local tumour control were end points of the study. Statistical analysis of the experiments included evaluation of tumour regrowth and local tumour control.

Results

Combined treatment with irradiation and lexatumumab led to a pronounced tumour regrowth-delay when compared to irradiation alone. The here presented long-term experiments revealed a highly significant rise of local tumour control for normoxic (ambient) (p = 0. 000006) and hypoxic treatment (p = 0. 000030).

Conclusion

Our data show that a combination of the pro-apoptotic antibody lexatumumab with irradiation reduces tumour regrowth and leads to a highly increased local tumour control in a nude mouse model. This substantial effect was observed under ambient and more pronounced under hypoxic conditions.
Appendix
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Metadata
Title
Combined treatment with lexatumumab and irradiation leads to strongly increased long term tumour control under normoxic and hypoxic conditions
Authors
Patrizia Marini
Dorothea Junginger
Stefan Stickl
Wilfried Budach
Maximilian Niyazi
Claus Belka
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2009
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-4-49

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