Mesenchymal Stem Cell-based Therapy for Treatment of Bone Metastases in Breast Cancer
Abstract
Bone metastasis remains an incurable condition in breast cancer patients and new therapeutic methods are urgently needed. In this study, bone marrow-derived mesenchymal stem cells (BMMSCs), with intrinsically homing capability towards tumor wounds, are selected as a natural vehicle to deliver anti-tumor agents into the bone lesions. However, due to MSCs dual roles in pre-clinical models, MSC-delivered targeted therapy could be potentially impaired by their intrinsic tumor-promoting effects. Therefore we will try to ablate the major tumor-promoting mechanisms in MSCs to build a more effective cell-based tumoricidal vehicle in treating metastatic breast cancer. During the reporting period, in Aim 1 we have measured the engraftment efficiency and safety of the genetically engineered BM-MSCs in vivo, and then we optimized the administration routes and timing of these engineered MSCs for better therapeutic effects. In Aim 2, we found that the adoptive transfer of engineered BMMSC spotentially accelerated the bone local T cell expansion, and the immune checkpoint inhibitors were able to improve the therapeutic effect of BM-MSC treatment in vivo. In the last Aim, we have constructed engineered human BM-MSCs and will apply them to treat bone metastases of human breast cancer cells in humanized mice model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2019
- Accession Number
- AD1080072
Entities
People
- Guangwen Ren