Poster Sessions

CANCER-12

Yu-an Yang

D. Weinberg, Y. Yang, K. Corps, S. Hoover, M. Simpson, L. Wakefield

Combination of Anti-TGF-Beta Antibody (1D11) and Paclitaxel Treatment Can Reduce Metastatic Burden in Murine Breast Cancer Models

TGF-beta has been implicated in a wide range of biological processes, especially those relating to development and cellular homeostasis. TGF-beta plays a complex role in tumorigenesis. In the early stages of oncogenesis TGF-beta exhibits a number of tumor suppressive effects. Yet, paradoxically, in more advanced cancer environments, TGF-beta has been shown to act as a pro-metastatic factor and a marker of poor prognosis. Despite this complex dual role, it has previously been shown that antagonizing TGF-beta in preclinical systems can increase survival and decrease metastatic burden. Here, we have used the 4T1 transplantable breast cancer model to assess combination therapy approaches to improve therapeutic efficacy of a monoclonal anti-TGF-beta antibody (1D11). We have shown that combining 1D11 with the chemotherapeutic paclitaxel provides added therapeutic benefit and we are exploring underlying mechanisms. 1D11 may counter the deleterious effects of increased TGF-beta production associated with chemotherapy, while paclitaxel may serve to potentiate the immune-mediated mechanism of 1D11. The results suggest an increased benefit in combining these two treatment options.