Novel Tumor Antigen-Specific Monoclonal Antibody-Based Immunotherapy to Eradicate Both Differentiated Cancer Cells and Cancer-Initiating Cells in Solid Tumors

A growing body of experimental and clinical evidence strongly suggests that the resistance of cancer-initiating cells (CICs) to conventional therapies represents a major obstacle to the successful treatment of a malignant disease. To overcome this limitation a novel combinatorial tumor antigen (TA)-specific monoclonal antibody (mAb) strategy has been developed. In this strategy TA-specific mAbs are combined with chemotherapeutic agents and/or small molecules that inhibit aberrantly activated signaling pathways in cancer cells and especially in CICs. The in vitro results we have obtained indicate that this strategy is very effective in eradicating both differentiated cancer cells and CICs in several types of malignant disease. If the in vitro results have in vivo relevance, the strategy we have designed may have an impact on the treatment of malignant diseases. (C) 2014 Published by Elsevier Inc.