Routes of delivery influence bacterial therapeutic efficacy 9030

Abstract Description Pancreatic cancer (PanC) remains one of the leading causes of cancer-related deaths worldwide. The current standard of care is ineffective and accompanied by significant side effects. Engineering suitable drug delivery systems can reduce toxic side effects and enhance therapeutic effectiveness. Bacterial-based therapeutics are re-emerging as promising solutions to address urgent clinical needs by targeting tumors and stimulating immune responses. Here we report a genetically attenuated strain of Brucella melitensis (BmΔvjbR) that homes to tumor tissue and potentiates the tumor immune microenvironment. Initial efficacy studies showed that BmΔvjbR reduced tumor size when administrated via tail vein in a syngeneic mouse model of PanC. Tail vein injections are time-consuming, require highly trained personnel and bear a success rate of 75 to 90%. Understanding optimal delivery is critical for maximizing BmΔvjbR therapeutic potential and minimizing side effects. In this study, we investigated alternative routes (intraperitoneal, intramuscular, intranasal) by evaluating tumor growth and mouse survival. Intraperitoneal delivery achieved similar efficacy results to intravenous administration with improved survival outcomes and no associated toxicity. Our findings indicate that intraperitoneal delivery is safe and effective, allowing time-efficient and reliable systemic administration which is essential for maximizing bacterial therapeutic efficacy. Funding Sources Advanced Research Projects Agency for Health (ARPA-H) grant 1AY1AX000010-01 Topic Categories Vaccines and Immunotherapy (VAC)