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Cancer Lett. 2017 Aug 28;402:32-42. doi: 10.1016/j.canlet.2017.05.003. Epub 2017 May 19.

Immunoproapoptotic molecule scFv-Fdt-tBid modified mesenchymal stem cells for prostate cancer dual-targeted therapy.

Author information

1
Department of Urology, Tang Du Hospital, The Fourth Military Medical University, Shaanxi, Xian, 710038, China; Department of Urology, Xi Jing Hospital, The Fourth Military Medical University, Shaanxi, Xian, 710032, China.
2
Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Shaanxi, Xian, 710032, China.
3
Department of Respiratory Medicine, The Third Hospital of Xi'an, Shaanxi, Xian, 710018, China.
4
Department of Laboratory, Xi Jing Hospital, The Fourth Military Medical University, Shaanxi, Xian, 710032, China.
5
Department of Urology, Xi Jing Hospital, The Fourth Military Medical University, Shaanxi, Xian, 710032, China.
6
Department of Urology, Tang Du Hospital, The Fourth Military Medical University, Shaanxi, Xian, 710038, China. Electronic address: duxjhw@fmmu.edu.cn.
7
Department of Urology, Xi Jing Hospital, The Fourth Military Medical University, Shaanxi, Xian, 710032, China. Electronic address: docwgj@sina.com.

Abstract

Highly efficient target therapy is urgently needed for prostate cancer with overexpression of γ-seminoprotein (γ-SM). Recent studies indicated that mesenchymal stem cells (MSCs) are attractive candidate for cell-based, targeted therapy due to their tumor tropism. Here we designed a dual-target therapeutic system in which MSCs were engineered to produce and deliver scFv-Fdt-tBid, a novel γ-SM-targeted immunoproapoptotic molecule. Such engineered MSCs (MSC.scFv-Fdt-tBid) would home to tumor sites and release the fusion protein to induce the apoptosis of prostate cancer cells. Our data demonstrated that scFv-Fdt-tBid showed a selective, potent and dose-dependent inhibition for γ-SM-positive cells (LNCaP, C4-2, 22Rv1) rather than γ-SM-negative cells and MSCs. Importantly, MSC.scFv-Fdt-tBid caused cell death through an apoptosis-dependent manner. Further, the tropism of MSC.scFv-Fdt-tBid to prostate cancer was verified both in vitro and in vivo. Finally, the in vivo experiments demonstrated that MSC.scFv-Fdt-tBid significantly inhibited γ-SM-positive tumor growth without toxic side effects. Collectively, this study represented a novel immunoproapoptotic molecule scFv-Fdt-tBid for γ-SM-positive tumors and demonstrated the therapeutic efficiency and safety of scFv-Fdt-tBid-modified MSCs against prostate cancers.

KEYWORDS:

Dual-target therapy; Immunoproapoptotic; MSCs; Prostate cancer

PMID:
28529067
DOI:
10.1016/j.canlet.2017.05.003
[Indexed for MEDLINE]

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