A yeast-based oral therapeutic delivers immune checkpoint inhibitors to reduce intestinal tumor burden
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.
Authors
- Jeanne Tung (ORCID: https://orcid.org/0000-0001-5949-3717)
- Bejan Mahmud (ORCID: https://orcid.org/0000-0002-5362-4920)
- James C. Liao (ORCID: https://orcid.org/0000-0002-4580-7276)
- Olivia N. Rebeck (ORCID: https://orcid.org/0000-0002-2220-3218)
- Jerome Prusa (ORCID: https://orcid.org/0000-0002-7963-5636)
- Mark G. Gorelik (ORCID: https://orcid.org/0000-0003-0161-2474)
- Gautam Dantas (ORCID: https://orcid.org/0000-0003-0455-8370)
- Miranda J. Wallace (ORCID: https://orcid.org/0000-0003-3036-4545)
- Suryang Kwak (ORCID: https://orcid.org/0000-0002-5202-8326)
- LeMoyne Habimana-Griffin
- Sunaina Rengarajan
- Skye R. S. Fishbein (ORCID: https://orcid.org/0000-0002-9554-1170)
- Beth A. Helmink (ORCID: https://orcid.org/0000-0002-8206-0351)
- Esse M. Evbuomwan (ORCID: https://orcid.org/0000-0002-3079-5575)
- Bin Wang (ORCID: https://orcid.org/0000-0002-4467-4176)
- Erick S Ramirez Tovar
- Jie Ning (ORCID: https://orcid.org/0000-0002-2063-7696)
- Rohin Mehta
- David Zahrah
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Washington University in St. Louis (US)
Publication Details
- Journal
- Cell chemical biology
- Published
- 2024-11-20
- DOI
- https://doi.org/10.1016/j.chembiol.2024.10.013
- Citations
- 30
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 7.01
Funders
- Radiological Society of North America
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Division of Cancer Prevention, National Cancer Institute
- National Institutes of Health
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Child Health and Human Development
- National Center for Complementary and Integrative Health