A yeast-based oral therapeutic delivers immune checkpoint inhibitors to reduce intestinal tumor burden

作者：Olivia N. Rebeck, Miranda J. Wallace, Jerome Prusa, Jie Ning, Esse M. Evbuomwan, Sunaina Rengarajan, LeMoyne Habimana-Griffin, Suryang Kwak, David Zahrah, Jason Tung, James C. Liao, Bejan Mahmud, Skye R. S. Fishbein, Erick S Ramirez Tovar, Rehan Mehta, Bin Wang, Mark G. Gorelik, Beth A. Helmink, Gautam Dantas · 发表于：Cell chemical biology · 年份：2024 · DOI：10.1016/j.chembiol.2024.10.013 · 被引用次数：36 · 研究领域：Gut microbiota and health、Cancer Immunotherapy and Biomarkers、Cancer Research and Treatments

Engineered probiotics are an emerging platform for in situ delivery of therapeutics to the gut. Herein, we developed an orally administered, yeast-based therapeutic delivery system to deliver next-generation immune checkpoint inhibitor (ICI) proteins directly to gastrointestinal tumors. We engineered Saccharomyces cerevisiae var. boulardii (Sb), a probiotic yeast with high genetic tractability and innate anticancer activity, to secrete "miniature" antibody variants that target programmed death ligand 1 (Sb_haPD-1). When tested in an ICI-refractory colorectal cancer (CRC) mouse model, Sb_haPD-1 significantly reduced intestinal tumor burden and resulted in significant shifts to the immune cell profile and microbiome composition. This oral therapeutic platform is modular and highly customizable, opening new avenues of targeted drug delivery that can be applied to treat a myriad of gastrointestinal malignancies.