Target therapy of multiple myeloma by PTX-NPs and ABCG2 antibody in a mouse xenograft model

Abstract

// Cuiping Yang 1, * , Fei Xiong 2, * , Jun Dou 1, * , Jun Xue 3 , Xi Zhan 4 , Fangfang Shi 5 , Miao Li 1 , Songyan Wu 1 , Shouhua Luo 2 , Tianzhu Zhang 2 , Yu Zhang 2 , Ji Ming 2 , Ning Gu 2 1 Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210009, China 2 School of Biological Science & Medical Engineering & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210096, China 3 Department of Hematology, Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China 4 The Center for Vascular and Inflammatory Diseases, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA 5 Department of Oncology, Zhongda Hospital, Southeast University, Nanjing 210009, China * These authors have contributed equally to this work Correspondence to: Jun Dou, e-mail: njdoujun@seu.edu.cn Ning Gu, e-mail: guning@seu.edu.cn Keywords: multiple myeloma, cancer stem cells, paclitaxel, nanoparticles, ATP-binding cassette sub-family G member 2 Received: May 01, 2015      Accepted: July 06, 2015      Published: July 15, 2015 ABSTRACT Multiple myeloma (MM) remains to be an incurable disease. The purpose of this study was to evaluate the effect of ABCG2 monoclonal antibody (McAb) combined with paclitaxel (PTX) conjugated with Fe 3 O 4 nanoparticles (NPs) on MM progressed from cancer stem cells (CSCs) in non-obese-diabetic/severe-combined-immunodeficiency (NOD/SCID) mouse model. Mice were injected with MM CSCs as marked by CD138 − CD34 − phenotypes through tail veins. The developed MM mice were examined by micro-computer tomography scanning, ultrasonography and enzyme-linked immunosorbent analysis. These mice were then intravenously treated with different combinations of NPs, PTX, McAb, PTX-NPs and melphalan/prednisone once a week for four weeks. The injected mice developed characteristic MM-associated syndromes, including lytic bone lesions, renal damages and proteinuria. All the treated mice showed decrease in bone lesions, renal damages and anemia but increase in apoptosis compared with the mice treated with NPs only. In particular, the treatment with ABCG2 McAb plus PTX-NPs induced the strongest therapeutic response and had an efficacy even better than that of melphalan/prednisone, a conventional regimen for MM patients. These data suggest that PTX-NPs with ABCG2 McAb can be developed into potential treatment regimens for patients with relapsed/refractory MM.