Monoclonal antibodies against human cancer stem cells

Abstract

Cancer stem cells (CSCs) are a subpopulation of tumor cells that display self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of cancer cells that comprise the tumor. CSCs exhibit intrinsic mechanisms of resistance to modern cancer therapeutics, allowing them to survive current cancer therapies and to initiate tumor recurrence and metastasis. Various cell surface and transmembrane proteins expressed by CSCs, including CD44, CD47, CD123, EpCAM (CD326), CD133, IGF receptor I, and proteins of the Notch and Wnt signaling pathways have been identified. Recently, monoclonal antibodies and antibody constructs raised against these CSC proteins have shown efficacy against CSCs in human cancer xenograft mice, and some of them have demonstrated antitumor activity in clinical studies. Since current cancer therapies fail to eliminate CSCs, leading to cancer recurrence and progression, selective targeting of CSCs with monoclonal antibodies and antibody constructs may represent a novel therapeutic strategy against cancer.