Targeting of pancreatic cancer cells and stromal cells using engineered oncolytic Salmonella typhimurium

Area of Science:

• Oncology
• Microbiology
• Immunology

Background:

• Pancreatic cancer exhibits resistance to conventional therapies.
• Abundant cancer stromal cells and limited immune cell infiltration contribute to treatment resistance.

Purpose of the Study:

• To evaluate the efficacy of attenuated Salmonella typhimurium engineered to express cytolysin A (ClyA) as a targeted therapy for pancreatic cancer.
• To investigate the impact of ClyA-expressing Salmonella on the tumor microenvironment, including stromal cell reduction and immune cell infiltration.

Main Methods:

• Nude mice with subcutaneous or orthotopic human pancreatic tumors were intravenously injected with engineered Salmonella typhimurium expressing ClyA.
• Tumor microenvironment analysis included monitoring stromal cell markers and immune cell infiltration.
• Bacterial accumulation, proliferation, and ClyA secretion within tumor tissues were assessed.

Main Results:

• Engineered Salmonella typhimurium specifically accumulated and proliferated in tumor tissues.
• A single dose of ClyA-expressing Salmonella significantly inhibited pancreatic cancer growth in both subcutaneous and orthotopic models.
• Histological analysis showed reduced stromal cell markers and increased infiltration of neutrophils and macrophages into tumors.

Conclusions:

• ClyA-expressing Salmonella typhimurium effectively destroys both cancer stromal cells and cancer cells in preclinical models.
• This approach offers a novel strategy for combined anticancer and anti-stromal therapy in pancreatic cancer treatment.