Description:
Brief description
Inducible expression of T-bet in epithelial cells promotes apoptosis and can be used as an anti-cancer therapy.
Problem
Cancer remains a leading cause of mortality worldwide, with epithelial cell cancers such as colon cancer presenting significant treatment challenges. Traditional approaches like chemotherapy and radiation therapy, while widely used, often lack specificity and can harm healthy cells, leading to severe side effects and limited efficacy against aggressive tumors. This has driven the need for more precise and controlled therapeutic strategies that can specifically target cancer cells while minimizing damage to normal tissues.
Solution
USC inventors developed a system to induce expression of T-bet (T-box transcription factor) in epithelial cells, offering a targeted approach to cancer treatment. It involves the delivery of viral vectors containing the T-bet coding sequence and promoter elements that regulate T-bet expression in a doxycycline-controlled manner. T-bet was found to modify ion channel and transporter levels in gut epithelial cells, promoting dehydration and ultimately leading to increased apoptosis. Overexpression of T-bet demonstrated significant efficacy in colon cancer models, achieving cell death and tumor shrinkage and in vivo.
Advantages
• Effective elimination of in vivo tumors: Significantly reduced tumor volume in BALB/c and NSG mice
• Controllable and specific tumor killing: Suitable for targeted delivery to cancer cells via oncolytic viruses and enables doxycycline-inducible expression of T-bet
• Novel approach for cancer therapy: Leverages a newly identified role of T-bet in promoting epithelial cell apoptosis
Applications
• Anti-cancer therapy for epithelial cell tumors
Supporting Figure
Figure 7d of published manuscript: Tumor growth curves from BALB/c mice injected with Tet-O-T-bet transduced or WT control CT-26 colon cancer cells. Mice were continuously treated with doxycycline water solution from day 7. (Student’s t test *p<0.05; **p<0.01; ***p<0.001)