Probiotic neoantigen delivery vectors for precision cancer immunotherapy

Andrew Redenti, Jongwon Im, Benjamin Redenti, Fangda Li, Mathieu Rouanne, Zeren Sheng, William Sun, Candice R. Gurbatri, Shunyu Huang, Meghna Komaranchath, YoungUk Jang, Jaeseung Hahn, Edward R. Ballister, Rosa L. Vincent, Ana Vardoshivilli, Tal Danino () and Nicholas Arpaia ()
Additional contact information
Andrew Redenti: Vagelos College of Physicians and Surgeons of Columbia University
Jongwon Im: Columbia University
Benjamin Redenti: Vagelos College of Physicians and Surgeons of Columbia University
Fangda Li: Vagelos College of Physicians and Surgeons of Columbia University
Mathieu Rouanne: Vagelos College of Physicians and Surgeons of Columbia University
Zeren Sheng: Columbia University
William Sun: Columbia University
Candice R. Gurbatri: Columbia University
Shunyu Huang: Columbia University
Meghna Komaranchath: Columbia University
YoungUk Jang: Columbia University
Jaeseung Hahn: Columbia University
Edward R. Ballister: Vagelos College of Physicians and Surgeons of Columbia University
Rosa L. Vincent: Columbia University
Ana Vardoshivilli: Columbia University
Tal Danino: Columbia University
Nicholas Arpaia: Vagelos College of Physicians and Surgeons of Columbia University

Nature, 2024, vol. 635, issue 8038, 453-461

Abstract: Abstract Microbial systems have been synthetically engineered to deploy therapeutic payloads in vivo1,2. With emerging evidence that bacteria naturally home in on tumours3,4 and modulate antitumour immunity5,6, one promising application is the development of bacterial vectors as precision cancer vaccines2,7. Here we engineered probiotic Escherichia coli Nissle 1917 as an antitumour vaccination platform optimized for enhanced production and cytosolic delivery of neoepitope-containing peptide arrays, with increased susceptibility to blood clearance and phagocytosis. These features enhance both safety and immunogenicity, achieving a system that drives potent and specific T cell-mediated anticancer immunity that effectively controls or eliminates tumour growth and extends survival in advanced murine primary and metastatic solid tumours. We demonstrate that the elicited antitumour immune response involves recruitment and activation of dendritic cells, extensive priming and activation of neoantigen-specific CD4+ and CD8+ T cells, broader activation of both T and natural killer cells, and a reduction of tumour-infiltrating immunosuppressive myeloid and regulatory T and B cell populations. Taken together, this work leverages the advantages of living medicines to deliver arrays of tumour-specific neoantigen-derived epitopes within the optimal context to induce specific, effective and durable systemic antitumour immunity.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-08033-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:635:y:2024:i:8038:d:10.1038_s41586-024-08033-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-08033-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().