Bioengineered bacteria in cancer immunotherapy: mechanistic advances, therapeutic strategies and clinical potential.

Bioengineered bacteria have emerged as a transformative platform in cancer immunotherapy, offering unique opportunities for selective tumour targeting, immune modulation, and localised delivery of therapeutic molecules. Their natural ability to colonise hypoxic and necrotic tumour regions, which are typically inaccessible to conventional chemotherapeutics, makes them powerful candidates for precision oncology. Recent advances in synthetic biology, genetic engineering, and physicochemical modification have enabled the design of programmable bacterial systems capable of delivering cytokines, immune checkpoint inhibitors, cytotoxic proteins, prodrug-converting enzymes, nanoparticles, and photosensitizers with high spatial and temporal control. Moreover, engineering strategies such as virulence attenuation, ligand-receptor targeting, quorum-sensing circuits, and hypoxia-responsive promoters significantly enhance biosafety and tumour specificity while minimising systemic toxicity. Chemically, physically, and biologically modified bacteria are increasingly being integrated with chemotherapy, radiotherapy, photodynamic therapy, and photothermal therapy, resulting in potent multimodal synergies that overcome tumour heterogeneity and immunosuppression. Despite remarkable progress, several challenges, including immune clearance, genetic stability, toxicity risks, and variability across tumour microenvironments, continue to limit clinical translation. This review provides a comprehensive overview of recent advancements in bacterial bioengineering, therapeutic strategies, combination approaches, and current limitations, offering critical insights into the design of next-generation living therapeutics for durable, personalised cancer immunotherapy.