Artikel
Combination of standard chemotherapy with MBT-0206 enhances the anti-tumor efficacy in a highly metastatic human pancreatic cancer mouse model
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Autoren
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Armine Papyan
- Chirurgische Klinik und Poliklinik-Großhadern, LMU München, München, Deutschland
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A. Werner
- Munich Biotech AG, Neuried, Deutschland
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I. Ischenko
- Chirurgische Klinik und Poliklinik-Großhadern, LMU München, München, Deutschland
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M. Teifel
- Munich Biotech AG, Neuried, Deutschland
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U. Michaelis
- Munich Biotech AG, Neuried, Deutschland
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K.W. Jauch
- Chirurgische Klinik und Poliklinik-Großhadern, LMU München, München, Deutschland
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C.J. Bruns
- Chirurgische Klinik und Poliklinik-Großhadern, LMU München, München, Deutschland
| Veröffentlicht: | 7. Oktober 2004 |
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Gliederung
Text
Introduction
Treatment of pancreatic cancer is still an unsolved problem because of the limited efficacy of systemic chemotherapy. MBT-0206 is a new anti-cancer agent which targets the neovascular endothelial cells of the tumor vasculature [Ref. 1], [Ref. 2]. It is composed of paclitaxel bound to a lipid complex (EndoTAG™), which has been shown to preferentially accumulate in endothelial cells of pancreatic tumor vessels in transgenic RIP-Tag2 mice [Ref. 3]. In the current study we investigated the anti-cancer potential of a combination therapy of MBT-0206 with the standard chemotherapy gemcitabine against highly metastatic human pancreatic cancer (L3.6pl) growing orthotopically in nude mice.
Materials and methods
Tumor bearing animals were treated for 19 days either by i.v. injected MBT-0206 (5 mg/kg) three times a week, by i.p. injected gemcitabine (100 mg/kg) two times a week or by combination of both treatments.
Results
Preliminary results demonstrated that the bio-distribution of systemically injected fluorescently labelled EndoTAG™ showed highly selective accumulation in the tumor vessels compared to surrounding normal pancreas. Application of MBT-0206 resulted in a strong growth inhibition of primary pancreatic tumors with a tumor size of 46 % of the control size at the end of the treatment, which was similar to the efficacy of gemcitabine (47%). Combination therapy led to a strong enhancement of the anti-tumor activity, resulting in a tumor size of only 21 % of untreated control tumors. In addition, liver and lymph node metastasis were markedly reduced following therapy with MBT-0206 plus gemcitabine. Interestingly, a dose reduction of gemcitabine by 50% (50 mg/kg) resulted in a comparable therapeutic efficacy and better tolerability of the combination therapy.
Conclusion
In summary, these data demonstrate a strong anti-tumor activity of the anti-neovascular targeting agent MBT-0206. Furthermore, the efficacy of MBT-0206 is enhanced when used in combination with gemcitabine. Our results suggest that MBT-0206 as an anti-neovascular agent is a promising candidate for the treatment of pancreatic cancer.
