Engineered food-borne probiotics delivering checkpoint-inhibitor modulators

Engineered food-borne probiotics represent an emerging <i>food-oncomicrobiology</i> strategy that unites synthetic biology, nutrition, and cancer immunotherapy. Preclinical models demonstrate potent antitumor effects: <i>Lactococcus lactis</i> secreting soluble CD80-reduced tumor growth by 64%; <i>Escherichia coli Nissle 1917</i> producing PD-L1 nanobodies achieved complete regression in 50% of treated mice with a two-fold rise in CD8⁺IFNγ⁺TNFα⁺ T-cell infiltration; and <i>Lactobacillus plantarum</i> delivering IL-2 enhanced NK-cell activity 2.5-fold and extended survival by 30%. Clinical meta-analyses reveal that gut-microbiome diversity increases checkpoint-inhibitor response by 40% and median progression-free survival by 12 months. A phase I trial in Non-Small Cell Lung Cancer (NSCLC) showed reduced immune-related colitis (from 14% to 6%) and higher response rates (36% vs 21%) with probiotic co-therapy. Remaining challenges in colonization and biosafety, together with advances in controllable genetic circuits, make edible biologics a promising, low-toxicity immunotherapeutic platform.