Engineered tumor-tropic mesenchymal stem cells as targeted therapeutic delivery systems for refractory Ovarian cancer.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The objective of this research was to develop a targeted clinically translatable stem cell-based system for the treatment of drug-resistant and metastatic ovarian cancer. To achieve this goal, we genetically engineered and isolated an adipose-derived stem cell (ASC) clone that expresses secretory human carboxylesterase-2 (shCE2) enzyme extracellularly and yeast cytosine deaminase: uracil phosphoribosyl transferase (yCD:UPRT) enzyme intracellularly for targeted combination enzyme/prodrug therapy. The shCE2 enzyme converts the prodrug irinotecan into its potent active metabolite SN-38, while yCD:UPRT transforms the prodrug 5-FC into the cytotoxic agent 5-FU. To evaluate the therapeutic potential of this system, we utilized ovarian cancer cells derived from patients with drug-resistant recurrent disease. All four lines exhibited sensitivity to SN-38 at sub-nanomolar concentrations, with a direct correlation observed between SN-38 sensitivity and expression levels of topoisomerase I. The cancer cells were subsequently xenografted into mice to establish metastatic intraperitoneal tumors. Following confirmation of active migration of the engineered ASCs toward the tumor sites through real-time bioluminescent imaging and immunohistochemistry, mice were treated either with prodrugs alone or in combination with the engineered ASCs. Therapeutic response and tumor relapses were assessed u

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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