Carboxyl Esterase-TRAIL Expressing Human Adipose Stem Cells Inhibit Tumor Growth in Castration-Resistant Prostate...

Area of Science:

• Oncology
• Stem Cell Therapy
• Gene Therapy

Background:

• Castration-resistant prostate cancer (CRPC) presents a significant clinical challenge.
• Current treatments often involve systemic toxicity.
• Targeted gene therapy using enzymes to activate prodrugs offers a potential strategy for reduced toxicity.

Purpose of the Study:

• To investigate the efficacy of genetically modified human adipose-derived stem cells (ADSC) expressing rabbit carboxylesterase (CE) and human TRAIL in suppressing CRPC tumor development.
• To evaluate the targeted migration and therapeutic effects of ADSC.CE.sTRAIL cells in CRPC mouse models.

Main Methods:

• Human adipose-derived stem cells (ADSC) were engineered to express rabbit CE and human TRAIL (ADSC.CE.sTRAIL).
• In vitro studies assessed the migration of ADSC.CE.sTRAIL cells toward PC3 prostate cancer cells and their cytotoxic effects under CPT-11 treatment.
• In vivo studies evaluated the anti-tumor efficacy of ADSC.CE.sTRAIL in CRPC-bearing mouse models.

Main Results:

• ADSC.CE.sTRAIL cells exhibited significantly enhanced directional migration toward PC3 cells.
• ADSC.CE.sTRAIL demonstrated superior 'suicide' effects, cytotoxicity, and apoptosis induction in cancer cells compared to control groups under CPT-11 treatment.
• In vivo, ADSC.CE.sTRAIL significantly inhibited tumor growth more effectively than CPT-11 monotherapy.

Conclusions:

• Engineered ADSC expressing CE and TRAIL show potent anti-tumor activity against CRPC.
• This approach offers a promising strategy for targeted drug activation and reduced systemic toxicity in CRPC treatment.
• Autologous ADSC hold potential for clinical trials in CRPC therapy.