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.

引用

页数：21

共 50 条

[11] The Impact of Tumor Volume Burden Reduction for Pediatric Solid Tumors by Immune Checkpoint Inhibitors
Saito, Takeshi
Fuchimoto, Yasushi
Fukui, Keisuke
Shimizu, Takahiro
Kuroda, Tatsuo
Hirabayashi, Takeshi
Hakamada, Kenichi
PEDIATRIC BLOOD & CANCER, 2020, 67
[12] Persistent Tumor Mutational Burden (pTMB) May Predict Response to Immune Checkpoint Inhibitors
Smith, Katherine E. R.
Markovic, Svetomir N.
CLINICAL CHEMISTRY, 2024, 70 (01) : 25 - 26
[13] Blood-based tumor mutational burden from circulating tumor DNA and immune checkpoint inhibitors in advanced prostate cancer.
Rauterkus, Grant
Hadadi, Agreen
Barnett, Reagan
Weipert, Caroline
Drusbosky, Leylah
Gao, Xin
Lilly, Michael B.
Bryce, Alan Haruo
Naqvi, Syed Arsalan Ahmed
Barata, Pedro C.
Bilen, Mehmet Asim
JOURNAL OF CLINICAL ONCOLOGY, 2022, 40 (06)
[14] Tumor Junction Burden and Antigen Presentation as Predictors of Survival in Mesothelioma Treated With Immune Checkpoint Inhibitors
Kosari, Farhad
Disselhorst, Maria
Yin, Jun
Peikert, Tobias
Udell, Julia
Johnson, Sarah
Smadbeck, James
Murphy, Stephen
McCune, Alexa
Karagouga, Giannoula
Desai, Aakash
Schaefer-Klein, Janet
Borad, Mitesh J.
Cheville, John
Vasmatzis, George
Baas, Paul
Mansfield, Aaron S.
JOURNAL OF THORACIC ONCOLOGY, 2022, 17 (03) : 446 - 454
[15] Discussion of tumor mutation burden as an indicator to predict efficacy of immune checkpoint inhibitors: A case report
Wu, Mingrui
Liang, Lan
Dai, Xiaotian
FRONTIERS IN ONCOLOGY, 2022, 12
[16] Tumor Mutational Burden as a Predictive Biomarker for Response to Immune Checkpoint Inhibitors: A Review of Current Evidence
Klempner, Samuel J.
Fabrizio, David
Bane, Shalmali
Reinhart, Marcia
Peoples, Tim
Ali, Siraj M.
Sokol, Ethan S.
Frampton, Garrett
Schrock, Alexa B.
Anhorn, Rachel
Reddy, Prasanth
ONCOLOGIST, 2020, 25 (01): : E147 - E159
[17] Tumor mutation burden predicts response and survival to immune checkpoint inhibitors: a meta-analysis
Wan, Linghong
Wang, Zhi
Xue, Jinmin
Yang, Huaju
Zhu, Yuxi
TRANSLATIONAL CANCER RESEARCH, 2020, 9 (09) : 5437 - 5449
[18] The value and inadequacy of tumor mutation burden on efficacy of immune checkpoint inhibitors in head and neck cancers
Ma, Hui-hui
Chen, Dong-sheng
Li, Si
Xiao, Ming-zhe
Qi, Chuang
ORAL ONCOLOGY, 2021, 117
[19] Exploring tumor mutational burden status and clinical benefit of immune checkpoint inhibitors in endometrial cancer
Valente, Ana
Gin, Amy
Wells, Allison
Ding, Kai
Moore, Kathleen
GYNECOLOGIC ONCOLOGY, 2022, 164 (01) : E15 - E16
[20] Tumor Mutational Burden and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Kim, Jong Yeob
Kronbichler, Andreas
Eisenhut, Michael
Hong, Sung Hwi
van der Vliet, Hans J.
Kang, Jeonghyun
Shin, Jae Il
Gamerith, Gabriele
CANCERS, 2019, 11 (11)

← 1 2 3 4 5 →