gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Combined treatment of colorectal tumors with apoptosis inducing TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 and radiotherapy: Additive effects in vitro and in vivo

Meeting Abstract

  • corresponding author presenting/speaker Patrizia Marini - Klinik für Radioonkologie, Tübingen, Deutschland
  • Sebastian Kauder - Klinik für Radioonkologie, Tübingen
  • Dirk Schiller - Klinik für Radioonkologie, Tübingen
  • Stefanie Denzinger - Klinik für Radioonkologie, Tübingen
  • Stefan Welz - Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Düsseldorf
  • Verena Jendrossek - Klinik für Radioonkologie, Tübingen
  • Wilfried Budach - Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Düsseldorf
  • Claus Belka - Klinik für Radioonkologie, Tübingen

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO445

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Veröffentlicht: 20. März 2006

© 2006 Marini et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Introduction: Humanized TRAIL receptor antibodies give opportunity to develop innovative molecular targeted antibody-based anticancer treatment protocols. TRAIL receptor antibodies from HGSI (Rockville, USA) are already subjects of clinical phase I/II trials. However, up to now, no data of a combined treatment with ionizing irradiation are available. Therefore, aim of the present study was evaluate putative beneficial effects of a TRAIL receptor based therapy in combination with ionizing radiation in vitro and in vivo.

Methods: Apoptosis induction in colorectal tumor cell lines Colo205, HCT 116 bax wt and bax -/- and HCT-15 after combined therapy (HGS-ETR1 or -2 0,01, 0,1, 1,0 mg/ml and 2,5,10 Gy) was determined by fluorescence microscopy and western blot analysis of caspase-8 und PARP. Growth delay-experiments were performed after combined therapy with fractionated irradiation (d1-5, SD 3 Gy) and the TRAIL-receptor antibodies (i.p. in 3 concentrations on d1, 4 und 8) with Colo 205 xenograft bearing NMRI nu/nu mice.

Results: HGS-ETR1 and HGS-ETR2 exerted dose dependent, additive effects in combination with irradiation in vitro and in vivo. These effects turned out to be at least partially bax dependent. In vivo data revealed a growth delay in tumor volume doubling time from 5.6 days in untreated animals to 71.0 days and 116.0 days after combined treatment with HGS-ETR1 (10 mg/kg body weight) and HGS-ETR2 (10 mg/kg body weight), respectively. HGS-ETR2 displayed increased antineoplastic activity when compared to HGS-ETR1.

Conclusion: The present study demonstrates for the first time additive effects of a combined treatment with the new agonistic TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 and irradiation in three different colorectal tumor cell lines in vitro. Importantly, a significant growth delay of xenograft tumors was also demonstrated. Thus, HGS-ETR1 and HGS-ETR-2 represent very promising new agents for an innovative molecular targeted combined anticancer therapy.