7P - Combination of cetuximab with radioimmunotherapy significantly enhances therapeutic response in colorectal cancer

Date 21 November 2014
Event ESMO Symposium on Immuno-Oncology 2014
Session Welcome reception and Poster viewing
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Cancer Immunology and Immunotherapy
Rectal Cancer
Presenter Vessela Vassileva
Authors V. Vassileva, M. Mazzantini, V. Rajkumar, M. Robson, A. Badar, M. Rashid, G. Boxer, B. Pedley
  • Oncology, UCL Cancer Institute, WC1E 6BT - London/UK

Abstract

Body

We explored a novel approach of combining radioimmunotherapy (RIT), using a humanized 131I-labelled anti-CEA antibody (131I-huA5B7) with cetuximab in colorectal cancer (CRC). The human CRC cell lines, SW1222 and LS174T, were used for in vitro studies, and to generate subcutaneous and hepatic xenografts in nude mice. There was a significant reduction in the clonogenic survival of both cell lines with RIT; however, SW1222 cells were more sensitive. Cetuximab significantly inhibited clonogenic survival, cell cycle dynamics, and prevented EGFR nuclear translocation in the SW1222 cells, but not in LS174T. In vivo, RIT alone resulted in selective tumour targeting, delayed tumor growth and prolonged survival in both models, without any observable toxicity. Cetuximab was only effective in SW1222 xenografts, and the combination treatment significantly enhanced therapeutic response compared with either monotherapy only in this model. Immunohistochemistry showed significantly reduced proliferation and increased apoptosis in tumours treated with RIT or in combination with cetuximab, which was also accompanied by an increase in markers of DNA damage response. Moreover, we demonstrate that this improved antitumour effect can be delivered using a clinically relevant activity of radionuclide and dose of cetuximab. Overall, our findings highlight the potential therapeutic benefit of combining cetuximab with RIT for the treatment of advanced CRC. This strategy could improve the treatment of residual disease post-operatively and ultimately prevent or delay recurrence. Furthermore, other CEA-expressing malignancies could also benefit from this approach.