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

被引：3
|
作者：
Rebeck, Olivia N. [1 ,2 ]
Wallace, Miranda J. [1 ,2 ]
Prusa, Jerome [1 ,2 ]
Ning, Jie [1 ,2 ]
Evbuomwan, Esse M. [1 ,2 ,3 ]
Rengarajan, Sunaina [1 ,4 ]
Habimana-Griffin, Lemoyne [1 ,5 ]
Kwak, Suryang [1 ,2 ]
Zahrah, David [1 ]
Tung, Jason [1 ]
Liao, James [1 ,2 ]
Mahmud, Bejan [1 ,2 ]
Fishbein, Skye R. S. [1 ,2 ]
Tovar, Erick S. Ramirez [1 ,2 ]
Mehta, Rehan [1 ,2 ]
Wang, Bin [1 ,2 ]
Gorelik, Mark G. [1 ,2 ]
Helmink, Beth A. [6 ]
Dantas, Gautam [1 ,2 ,3 ,7 ,8 ]
机构：
[1] Washington Univ, Sch Med, Edison Family Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pathol & Immunol, Div Lab & Genom Med, St Louis, MO 63110 USA
[3] Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USA
[4] Washington Univ, Sch Med, John T Milliken Dept Internal Med, Div Dermatol, St Louis, MO 63110 USA
[5] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA
[6] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA
[7] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
[8] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
来源：
CELL CHEMICAL BIOLOGY | 2025年 / 32卷 / 01期
基金：
美国国家卫生研究院;
关键词：
MONOCLONAL-ANTIBODY THERAPY; SACCHAROMYCES-BOULARDII; GUT MICROBIOME; RESISTANCE; CANCER; IMMUNOTHERAPY; MECHANISMS; PREVENTION; EFFICACY;
D O I：
10.1016/j.chembiol.2024.10.013
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
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页数：21
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