Engineered Lactobacillus expressing tumor-killing cytokines: a novel biotherapeutic

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 <i>Lactobacillus</i> 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 <i>Lactobacillus plantarum</i> secreting IL-12 reduces colorectal tumor volume by 65%, <i>L. casei</i> expressing TRAIL decreases pancreatic tumor mass by 40%, and <i>L. reuteri</i> 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 <i>Lactobacillus</i> as a novel, locally acting, and low-toxicity antitumor biotherapeutic with the potential to reshape next-generation cancer treatment.