Targeting the Microbiome to Enable Immunotherapeutic Efficacy in Pancreatic Carcinoma

ABSTRACT

Our goal is to perform clinical trials in PDA patients testing strategies to modulate the microbiome to enhance the efficacy for immunotherapy. However, the optimal regimen has not been defined. We will perform experiments in mouse PDA models and in human organotypic systems which are designed to define the most efficacious microbiome modulatory regimens - either antibiotics or probiotics - to combine with immunotherapy. In Aim 1 we will test the immune-activating and tumor-protective effects of specific antibiotic and probiotic regimens in mouse models of PDA and an innovative microfluidic-based organotypic model derived from freshly resected human PDA. In Aim 2 we will determine the regimen that most effectively synergizes with immunotherapy. Aim 3 will encompass the first clinical trial in PDA targeting the microbiome as a strategy to enable immunotherapeutic efficacy. Collectively, these Aims will lead to a new treatment paradigm for PDA patients that targets the microbiome.