Target therapy of multiple myeloma by PTX-NPs and ABCG2 antibody in a mouse xenograft model
Cuiping Yang1, Fei Xiong2, Jun Dou1
1Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210009, China.
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 Fe3O4 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.
Insights
A novel combination therapy using ABCG2 monoclonal antibody and paclitaxel-conjugated nanoparticles shows promise for treating multiple myeloma (MM). This new approach demonstrated superior efficacy compared to conventional treatments in preclinical models.
Area of Science:
- Oncology
- Nanomedicine
- Immunotherapy
Background:
- Multiple myeloma (MM) is an incurable hematologic malignancy.
- Cancer stem cells (CSCs) are implicated in MM progression and treatment resistance.
- Developing effective therapies for relapsed/refractory MM remains a significant challenge.
Purpose of the Study:
- To evaluate the therapeutic effect of combining an ABCG2 monoclonal antibody (McAb) with paclitaxel (PTX) conjugated to Fe3O4 nanoparticles (NPs).
- To assess this combination therapy in a mouse model of MM derived from cancer stem cells.
Main Methods:
- Establishment of a multiple myeloma cancer stem cell (MM CSC) model in NOD/SCID mice.
- Treatment of MM-bearing mice with various combinations: NPs, PTX, McAb, PTX-NPs, and melphalan/prednisone.
- Evaluation of therapeutic response using micro-computer tomography, ultrasonography, ELISA, and assessment of MM-associated syndromes.
Main Results:
- All tested treatments reduced bone lesions, renal damage, and anemia, and increased apoptosis compared to control.
- The combination of ABCG2 McAb and PTX-NPs exhibited the strongest therapeutic response.
- This novel combination therapy showed efficacy superior to the conventional melphalan/prednisone regimen.
Conclusions:
- Paclitaxel-conjugated nanoparticles combined with ABCG2 monoclonal antibody represent a promising therapeutic strategy for relapsed/refractory multiple myeloma.
- This approach warrants further investigation as a potential treatment for patients with difficult-to-treat MM.
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