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

Cancer Letters
Fengqi YanGuojun Wu

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...Continue Reading

Citations

Mar 16, 2018·Chemistry : a European Journal·Bishnu P JoshiMichelle E Farkas
Nov 6, 2018·The Journal of Craniofacial Surgery·Hua-Jiang DongLei Wang
Oct 27, 2017·Oncotarget·Billy Samuel HillAntonella Zannetti
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Jeanne Adiwinata PawitanDelvac Oceandy
Nov 19, 2020·Stem Cell Reviews and Reports·Jiayi ZhangYaming Wei
Mar 1, 2020·Drug Discovery Today·Yunfeng LinLei Zhang

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