Engineered Lactobacillus expressing tumor-killing cytokines: a novel biotherapeutic
Year: 2025
Type: article
Abstract: Cancer accounts for over 10 million deaths annually, with solid tumors responsible for nearly 90% of cases worldwide. Systemic cytokine administration remains limited by severe toxicity, high-dose interleukin-2 (IL-2) therapy induces grade 3–4 adverse effects in >60% of patients, and treatment-related mortality is around 4%. In this context, engineered Lactobacillus strains designed to express tumor-killing cytokines such as IL-12, IL-15, and TRAIL represent a novel biotherapeutic strategy that combines microbial safety with precision immune activation. Experimental evidence shows that Lactobacillus plantarum secreting IL-12 reduces colorectal tumor volume by 65%, L. casei expressing TRAIL decreases pancreatic tumor mass by 40%, and L. reuteri producing IL-15 enhances CD8+ T-cell infiltration by 45% and improves survival by 30% in murine models. These data illustrate that cytokine-expressing probiotics can replicate the efficacy of systemic cytokine therapy while avoiding dose-limiting toxicity. Integrating synthetic biology tools such as inducible promoters and biosafety kill switches further refines control and containment, making this a viable candidate for translational development. The convergence of immunotherapy and microbiome engineering thus establishes engineered Lactobacillus as a novel, locally acting, and low-toxicity antitumor biotherapeutic with the potential to reshape next-generation cancer treatment.
Source: Annals of Medicine and Surgery
Authors: Muhammad Shahid Mehmood, Maryam Abid, Fatima Hajj
Language: English
Subfield: Biotechnology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,850
OpenAlex ID: W4416951649