Injectable microgels containing genetically engineered bacteria for colon cancer therapy through programmed Chemokine...

Area of Science:

• Immunology
• Biotechnology
• Cancer Research

Background:

• Chemokines regulate immune cell activity in the tumor microenvironment, making them key targets for cancer immunotherapy.
• Sustained chemokine delivery to tumors is crucial for recruiting and activating immune cells to fight cancer.

Purpose of the Study:

• To engineer a bacterial cell factory for controlled, continuous production of chemokine CCL21.
• To evaluate the efficacy of encapsulated engineered bacteria for sustained chemokine delivery and anti-tumor effects.

Main Methods:

• Engineered bacteria using thioredoxin (Trx) fusion to reduce inclusion bodies and various promoters (pT7-LacO, pBV220, pDawn) to optimize CCL21 expression.
• Encapsulation of engineered bacteria within gelatin methacryloyl (GelMA) microgels for enhanced viability and retention.
• Assessment of tumor growth suppression in a mouse model.

Main Results:

• Successful continuous production of chemokine CCL21 by engineered bacteria.
• GelMA microgels maintained bacterial viability and prolonged intestinal retention.
• Sustained, localized CCL21 production effectively suppressed tumor growth.

Conclusions:

• Genetically engineered bacteria encapsulated in GelMA microgels offer a promising strategy for sustained chemokine delivery in cancer immunotherapy.
• This approach facilitates controlled chemokine production, enhancing immune cell recruitment and anti-tumor immune responses.