Immune-mediated approaches like BCG and oncolytic viruses show the most advanced clinical translation in bladder cancerLiving cancer therapies show promise for bladder cancer

Urinary bladder cancer (UBC) remains a major global health burden, with high recurrence rates and limited therapeutic options for patients who fail standard intravesical and systemic treatments. In recent years, Living Cancer Therapeutics (LCTs)—including bacteria-, virus-, and microbiome-based oncobiotics—emerged as innovative biological strategies capable of overcoming key limitations of conventional cancer therapies. This article is a narrative review aimed at mapping the mechanistic landscape, historical development, and translational progress of LCTs in UBC. Five interrelated mechanisms were identified through which oncobiotics exert therapeutic effects: (i) direct tumor destruction via bacterial colonization, cytolysis, and metabolic deprivation; (ii) immune system modulation through innate and adaptive immune activation; (iii) engineered drug delivery and synthetic biology enabling programmable, tumor-restricted payload release; (iv) oncolytic virotherapy combining selective tumor lysis with immune priming; and (v) microbiome-driven immune modulation influencing treatment responsiveness. Although conceptually distinct, these mechanisms frequently overlap in practice, reflecting the multifunctional nature of living therapeutics. Clinical translation has progressed furthest for immune-mediated approaches such as Bacillus Calmette–Guérin (BCG) and selected oncolytic viral platforms, particularly in BCG-unresponsive UBC, although current evidence remains limited by small studies, heterogeneous endpoints, and insufficient long-term follow-up. Advances in genetic engineering and synthetic biology have enabled the development of increasingly sophisticated investigational platforms, including engineered oncolytic viruses, programmable bacterial vectors, and microbiome-based therapeutic strategies; however, most remain at an early preclinical or translational stage. UBC may represent a favorable setting for LCT development due to the accessibility of the bladder and the established use of intravesical therapies, although delivery efficiency and therapeutic durability remain important challenges. Despite encouraging early findings, significant limitations persist, including biological delivery barriers, host immune neutralization, interpatient heterogeneity, biosafety concerns, regulatory complexity, and the scarcity of late-phase randomized clinical data. Further translational research, biomarker development, and long-term clinical evaluation will therefore be required to determine the future role of LCTs in UBC management.