4.6 Review

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

Journal

EXPERT OPINION ON DRUG DELIVERY
Volume 18, Issue 11, Pages 1627-1642

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/17425247.2021.1960309

Keywords

Anti-cancer drug; cancer therapy; cell-based drug delivery; cell engineering; mesenchymal stem; stromal cells; targeting; tumor homing

Funding

  1. Japan Society for the Promotion of Science (JSPS) [15K18850, 17K15437, 20J14253]
  2. Grants-in-Aid for Scientific Research [20J14253, 17K15437, 15K18850] Funding Source: KAKEN

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Although numerous preclinical studies have shown significant anti-tumor effects of MSC-based cancer therapy, several clinical trials have failed to demonstrate consistent results, indicating limited therapeutic effects. In order to achieve successful clinical outcomes with MSC-based cancer therapy, it is important to address interdonor heterogeneity of administered MSCs, improve tumor-homing efficiency, and optimize drug delivery from MSCs to cancer cells.
Introduction Drug delivery to solid tumors remains a significant therapeutic challenge. Mesenchymal stem/stromal cells (MSCs) home to tumor tissues and can be employed as tumor targeted drug/gene delivery vehicles. Reportedly, therapeutic gene- or anti-cancer drug-loaded MSCs have shown remarkable anti-tumor effects in preclinical studies, and some clinical trials for assessing therapeutic MSCs in patients with cancer have been registered. Areas covered In the present review, we first discuss the source and interdonor heterogeneity of MSCs, their tumor-homing mechanism, and the route of MSC administration in MSC-based cancer therapy. We then summarize the therapeutic applications of MSCs as a drug delivery vehicle for therapeutic genes or anti-cancer drugs and the drug delivery mechanism from drug-loaded MSCs to cancer cells. Expert opinion Although numerous preclinical studies have revealed significant anti-tumor effects, several clinical trials assessing MSC-based cancer gene therapy have failed to demonstrate corroborative results, documenting limited therapeutic effects. Notably, a successful clinical outcome with MSC-based cancer therapy would require the interdonor heterogeneity of administered MSCs to be resolved, along with improved tumor-homing efficiency and optimized drug delivery efficiency from MSCs to cancer cells.

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