Abstract 2443: Tetraspanin CD151 as a target for antibody-based cancer therapy

Abstract

Abstract The tetraspanin CD151 is known to be functionally linked to cancer metastasis. In human, increased expression of CD151 is indicative of a poor prognosis in different cancer types. Whereas its precise mechanism of action remains obscure, CD151 was shown to regulate cell motility and adhesion through association with laminin-binding integrins such as α3β1 or α6β4, and more recently the communication between endothelial and tumor cells. Overexpression of CD151 in tumor cells enhances cell migration, cell invasion and experimental metastasis. Silencing of CD151 with specific siRNA was shown to delay tumour formation in vivo in a mouse model of breast cancer. Several anti-CD151 monoclonal antibodies (Mabs) were shown to display anti-metastatic activity in vivo. Inhibition of metastasis was not attributed to any effect of these Mabs on tumor cell growth but was essentially linked to inhibition of cell motility. However, a more direct effect could be expected. For these reasons, we generated different anti-CD151 Mabs via immunisation with transfectant cells and evaluated their anti-tumor activity in xenograft and orthotopic mouse models to further investigate the role of CD151 in cancer progression in vivo. Interestingly, anti-CD151 Mabs inhibited potently primary tumor growth in different xenograft models including prostate, lung and breast cancer models. These results demonstrate that CD151 could be of importance for controlling tumor cell proliferation. In addition, as anticipated, we showed that anti-CD151 Mabs were also able to inhibit metastasis in vivo in an orthotopic A549 lung cancer model with well characterized lung metastases. The mechanism of action of these Mabs on tumor cells is under investigation and preliminary in vitro data will be presented. Altogether, our results strongly suggest that CD151 could function at multiple cancer stages, including not only metastasis cascade steps but also earlier steps of primary tumor growth, reinforcing thus the interest of this innovative target in oncology. Mabs targeting CD151 may be of significant interest for cancer biotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2443.