W233 - Oral Immunization with Highly Attenuated Listeria-based Cancer Vaccines Elicits Protective Gastrointestinal Focused Immunity in Colorectal Cancer

Xinyuan Lei1, Yue Zhang1, Charlie Chuang2, Timothy Chu1, Aybuke Garipcan2, Zhijuan Qiu1, Xinran Li1, Kadir A. Ozler2, Semir Beyaz2, Brian S. Sheridan1
1. Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794
2. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724

Gastrointestinal (GI) cancers, including colorectal, small intestine, and pancreatic cancer are a major public health issue worldwide. Commonly used treatment strategies in the clinic include surgery, radiotherapy, and chemotherapy that may provide short-term control of tumors. Cancer vaccines have recently emerged as a promising immunotherapeutic strategy to eliminate tumors while providing long-lasting protection. Listeria monocytogenes (Lm) is an intracellular bacterium that stimulates potent innate and adaptive immune responses that are critical for tumor control. Indeed, Lm-based intravenous (i.v.) vaccines have emerged as a promising strategy to elicit a robust tumor-reactive CD8 T cell response. Despite some reported therapeutic efficacy in clinical trials for various solid tumors, this approach requires improvements.

Our prior research demonstrated that foodborne Lm infection of mice induced qualitatively and quantitatively superior CD8 T cell responses that were focused in GI tissues when compared to i.v. infection. Based on this finding, we hypothesized that oral Lm immunization would provide better protection against GI tumors. In this study, we used a modified Lm strain that contains a mutation in the epithelial invasion protein InlA, allowing efficient invasion of murine intestinal epithelium to mimic oral immunization in humans. our findings indicate that highly attenuated Lm-based vaccines elicit robust CD8 T cell responses and demonstrate an excellent safety profile when administered by oral immunization of mice. More importantly, oral Lm immunization provided rapid antigen-specific protection in an orthotopic transplant model of colorectal cancer with a tumor rejection rate of 92%.