Bugs delivering drugs: Listeria monocytogenes-mediated cytotoxin delivery enhances anti-tumor activity in colorectal cancer.

Targeted drug delivery is among the fastest growing fields in cancer therapy. Advances in delivery have resulted in developments like antibody-drug conjugates (ADCs) and drug-loaded nanoparticles. Delivery, however, is hampered by target resistance, induced immunosuppression, and low tumor penetration. Listeria monocytogenes (LM) is a Gram-positive intracellular bacterium being investigated in preclinical and clinical trials as a therapeutic cancer vaccine platform. However, limited work has explored LM as a cytotoxin delivery vehicle. Here, we show that LM can deliver cytotoxin cargo resulting in increased cytotoxicity in vitro and reduced tumor growth in vivo in a microsatellite-stable (MSS) colorectal cancer (CRC) model. LM delivery of saporin dramatically improved cytotoxicity over SN38/Dox-ADC cargo. Reduced MSS CRC tumor growth was dependent on LM-mediated delivery of saporin and correlated with high immune infiltration. These results demonstrate efficacious cytotoxin delivery using LM and establish precedent for LM as a delivery vehicle for cytotoxic agents.