Anti-ABCG2 Monoclonal Antibody in Combination with Paclitaxel-Nanoparticles Against Cancer Stem-Like Cell Activity in Multiple Myeloma

Abstract 5044

In spite of the past efforts and progress made in treatment multiple myeloma (MM), most MM patients have eventually relapsed and died of the cancer. Cancer stem cells (CSCs) are considered responsible for continued growth and recurrence of cancer. The purpose of this study was to investigate the effects of anti-ABCG2 monoclonal antibody (mAb) in combination with paclitaxel-Fe₃O₄ nanoparticles (PTX-NPs) on CD138⁻CD34⁻MM cancer stem-like cells (MM CSCs) isolated from MM cell line JJN3. In our results, the MM CSCs expressed higher levels of the ABCG2 transporter, exhibited high proliferative, clonogenic and migratory potency, and demonstrated strong drug resistance and tumorigenicity when compared to non-CD138⁻CD34⁻MM cells. Incubation of mAb with PTX-NPs remarkably induced G/M cell cycle arrest, and increased synergistic induction of MM CSC apoptosis compared with incubation with PTX-NPs or PTX or mAb alone. More importantly, mAb in combination with PTX-NPs led to a significant reduction in the tumor volume, to a visible alleviation of murine lytic bone lesions and to a markedly increased survival rate in contrast to using a single agent in MM CSCs when it was transplanted to nonobese diabetic/severe combined immunodeficiency mice. Our study is the first to report on the anti-MM CSC activities by PTX-NPs as single agent or used together with mAb to treat MM. This finding from our study provides a rationale for future clinical trials.