A live biohybrid bacterial therapy based on engineered Serratia marcescens

Area of Science:

• Microbiology
• Immunology
• Biotechnology

Background:

• Bacterial therapeutics offer targeted cancer treatment, especially in hypoxic tumor regions.
• Current bacterial cancer therapies face challenges with safety and complex engineering.
• A safe, effective delivery platform using natural bacterial biosynthesis is needed.

Purpose of the Study:

• To develop an attenuated Serratia marcescens (S. marcescens) biohybrid platform for cancer therapy.
• To leverage S. marcescens' natural biosynthesis of prodigiosin for enhanced anti-cancer effects.
• To establish a safe, self-regulating, and precise cancer immunotherapy.

Main Methods:

• Engineering S. marcescens for high prodigiosin yield.
• Evaluating prodigiosin's anti-cancer activity and photosensitivity.
• Assessing the platform's efficacy in mouse models of melanoma and colorectal cancer.
• Analyzing immune responses, tumor cell death (mitophagy), and bacterial clearance.

Main Results:

• Engineered S. marcescens produced high levels of prodigiosin with intrinsic anti-cancer activity and near-infrared photosensitivity.
• The bacterial platform induced robust systemic immune responses, including T cell recruitment and memory.
• Tumor cell death was observed via mitophagy, and photothermal properties enabled light-controlled bacterial clearance.
• Significant anti-cancer effects were demonstrated in melanoma and colorectal cancer mouse models.

Conclusions:

• Attenuated S. marcescens serves as a versatile biohybrid platform for cancer immunotherapy.
• The platform utilizes natural prodigiosin biosynthesis for targeted cancer cell death and immune stimulation.
• This approach offers precise, safe, and self-regulating cancer treatment with controlled bacterial clearance.