Researchers at Dana-Farber Cancer Institute and the University of Michigan have engineered E. coli bacteria to enhance immunotherapy responses in advanced malignancies. The study, published in Nature Biotechnology, demonstrates that these modified bacteria can effectively target tumors, stimulate immune responses, and improve the efficacy of existing immunotherapies.
Engineered E. coli as a Tumor-Targeting Immunotherapy
The team, led by Dr. Romee and Dr. Jiahe Li, genetically modified gut-derived E. coli to express immune-activating cytokines on their surfaces. The rationale behind this approach is that E. coli bacteria tend to colonize hypoxic areas, including tumors. By engineering these bacteria to express immune-stimulating molecules, the researchers aimed to create a targeted immunotherapy that could induce potent anti-tumor responses.
Superior Anti-Tumor Responses in Preclinical Models
The engineered E. coli, specifically those displaying murine decoy-resistant IL18, demonstrated superior anti-tumor responses compared to immune checkpoint inhibitor therapy in mice. The study reported a 50-60% cure rate in mice treated with the modified bacteria. Furthermore, the researchers observed a synergistic effect when combining the engineered bacteria with immune checkpoint inhibitors, suggesting a potential for improved treatment outcomes in clinical settings.
Enhanced Immune Cell Activity and Tumor Infiltration
Analysis of treated tumor tissues revealed increased activity and infiltration of CD8+ T cells and NK cells. This indicates that the engineered E. coli effectively stimulated the immune system, leading to a more robust anti-tumor response. Additionally, the therapy enhanced the therapeutic efficacy of mesothelin-targeting CAR NK cells in mice, suggesting that the bacteria act as a "tumor GPS" for systemically infused NK cells.
Potential for Clinical Translation
The study also demonstrated the safety and efficacy of this approach in multiple hard-to-treat tumors, including mesothelioma. These findings support the evaluation of this approach, either alone or in combination with other immunotherapeutic strategies, in early-phase clinical trials. According to the researchers, this novel strategy addresses a critical unmet need in cancer therapy by enhancing the precision and effectiveness of immunotherapy.
