Bacteria-Mediated Cancer Therapy and Immunotherapy

Bacteria-mediated cancer therapy harnesses the innate tumour­tropic properties of certain bacterial species to selectively colonise and eradicate malignant tissue. Attenuated or genetically engineered strains can be programmed to deliver cytotoxic agents, prodrug-converting enzymes or immune-stimulating molecules directly within the tumour microenvironment, thereby minimising off-target toxicity. Synthetic biology approaches enable fine-tuning of bacterial behaviour through inducible gene circuits, surface engineering and incorporation of nanomaterials to control payload release and enhance metabolic functions. Crucially, the interaction between engineered microbes and host immunity can be leveraged to activate innate and adaptive responses, recruit effector cells and establish long-term immunological memory. Recent advances address key challenges in safety and delivery, including evasion of premature immune clearance, biocontainment mechanisms and tumour-specific accumulation. The field is rapidly evolving towards multifunctional living medicines that integrate targeted delivery, real-time control of bioactivity and robust activation of antitumour immunity, offering novel avenues for treating solid and metastatic cancers.

Research from Nature Portfolio

Programmable microbial encapsulation has emerged as a powerful strategy to optimise systemic delivery of therapeutic bacteria. Dynamic expression of capsular polysaccharides via synthetic gene circuits allows bacteria to transiently evade immune detection and then shed their capsule for effective clearance, resulting in higher tolerated doses and improved tumour colonisation in mouse models. Surface conjugation of tumour-specific aptamers represents another approach to boost intratumoral accumulation: controllable amidation chemistry anchors oligonucleotides on attenuated Salmonella, achieving multi-fold increases in localisation and enhanced activation of local immune responses. Separately, synthetic biology has been used to engineer non-pathogenic strains to deliver STING-agonists directly to antigen-presenting cells within tumours, eliciting potent innate signalling, generation of cytotoxic T-cell responses and durable tumour regression, all within a biocontained chassis suitable for clinical translation.

Bacteria-Mediated Cancer Therapy and Immunotherapy publication trend

The graph below shows the total number of articles in bacteria-mediated cancer therapy and immunotherapy across all publications each year (not limited to Nature Index journals).

Technical terms

Tumour microenvironment: The complex milieu of cancer cells, stromal elements, immune infiltrates, blood vessels and extracellular matrix that influences tumour progression and therapeutic response.

Antigen-presenting cell (APC): A specialised immune cell, such as a dendritic cell or macrophage, that processes and presents antigens to T lymphocytes to initiate adaptive immunity.

Capsular polysaccharides: Surface-expressed carbohydrate molecules that form a protective layer around bacterial cells, governing immune evasion and host interactions.

Biocontainment: Engineered safeguards within living therapeutics that restrict microbial survival or gene expression outside defined conditions, enhancing safety for clinical use.

References

1. Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy. Signal Transduction and Targeted Therapy (2024).
2. A programmable encapsulation system improves delivery of therapeutic bacteria in mice. Nature Biotechnology (2022).
3. Aptamer-assisted tumor localization of bacteria for enhanced biotherapy. Nature Communications (2021).
4. Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity. Nature Communications (2020).
5. Bacteria-cancer interactions: bacteria-based cancer therapy. Experimental & Molecular Medicine (2019).
6. Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities. Cancer Medicine (2019).