Orthogonally Engineered Bacteria Capture Metabolically Labeled Tumor Antigens to Improve the Systemic Immune Response in Irradiated Tumors DOI

Wen Xia,

Zhuo Feng, Yuchen Wang

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: 19(5), P. 5376 - 5391

Published: Jan. 31, 2025

In situ vaccination is considered a promising cancer immunotherapy strategy to elicit tumor-specific T cell response. Live bacteria effectively enhanced the immune response in irradiated tumors as it can activate multiple cells. However, adaptive remains low since lack efficient delivery of antigen dendritic cells (DCs). Here, we show that tumor antigens be metabolically labeled with azido groups situ, allowing for their specific capture by orthogonally engineered Salmonella via bioorthogonal chemistry. Subsequently, these are efficiently delivered DCs through active movement bacteria. Intratumorally injected captured and improved presentation DCs. This increased proportion antigen-specific CD8+ tumors, further resulting systemic antitumor effects bilateral melanoma mouse model. The were abrogated Batf3-/- mice or after depletion, indicating dependent on responses. Overall, our work presents combining bacterial engineering labeling, which may guide development vaccines future.

Language: Английский

Engineered Living Materials for Advanced Diseases Therapy DOI Open Access
Dong Xue, Wei Wu, Pei Pan

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown

Published: July 12, 2023

Abstract Natural living materials serving as biotherapeutics exhibit great potential for treating various diseases owing to their immunoactivity, tissue targeting, and other biological activities. In this review, the recent developments in engineered materials, including mammalian cells, bacteria, viruses, fungi, microalgae, plants, active derivatives that are used summarized. Further, future perspectives challenges of such material‐based discussed provide considerations advances biomedical applications.

Language: Английский

Citations

54
Bacterial therapies at the interface of synthetic biology and nanomedicine DOI
Jaeseung Hahn, Suwan Ding, Jongwon Im

et al.

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 2(2), P. 120 - 135

Published: Oct. 10, 2023

Language: Английский

Citations

47
Role of the microbiota in response to and recovery from cancer therapy DOI
Stephen J. Blake, Yochai Wolf, Ben Boursi

et al.

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(5), P. 308 - 325

Published: Nov. 6, 2023

Language: Английский

Citations

47
Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer DOI Creative Commons

Yueyue Fan,

Jiamin Ye, Yong Kang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(19)

Published: May 8, 2024

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective immunotherapy. Here, an intelligent treatment microrobot based on unique physiological structure and metabolic characteristics of

Language: Английский

Citations

36
Glioblastoma vaccines: past, present, and opportunities DOI Creative Commons
Zujian Xiong, Itay Raphael, Michael R. Olin

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 100, P. 104963 - 104963

Published: Jan. 5, 2024

Glioblastoma (GBM) is one of the most lethal central nervous systems (CNS) tumours in adults. As supplements to standard care (SOC), various immunotherapies improve therapeutic effect other cancers. Among them, tumour vaccines can serve as complementary monotherapy or boost clinical efficacy with immunotherapies, such immune checkpoint blockade (ICB) and chimeric antigen receptor T cells (CAR-T) therapy. Previous studies GBM have suggested that few neoantigens could be targeted due low mutation burden, single-peptide vaccination had limited control monotherapy. Combining diverse antigens, including neoantigens, tumour-associated antigens (TAAs), pathogen-derived optimizing vaccine design strategy may help improvement. In this review, we discussed current platforms, evaluated potential antigenic targets, challenges, perspective opportunities for

Language: Английский

Citations

31
Probiotic neoantigen delivery vectors for precision cancer immunotherapy DOI Creative Commons
Andrew Redenti, Jongwon Im,

Benjamin Redenti

et al.

Nature, Journal Year: 2024, Volume and Issue: 635(8038), P. 453 - 461

Published: Oct. 16, 2024

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

Language: Английский

Citations

30
The Multifaceted Role of Tissue-Resident Memory T Cells DOI
Susan N. Christo, Simone L. Park, Scott N. Mueller

et al.

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 317 - 345

Published: June 28, 2024

Regionalized immune surveillance relies on the concerted efforts of diverse memory T cell populations. Of these, tissue-resident (TRM) cells are strategically positioned in barrier tissues, where they enable efficient frontline defense against infections and cancer. However, long-term persistence these has been implicated a variety immune-mediated pathologies. Consequently, modulating TRM populations represents an attractive strategy for novel vaccination therapeutic interventions tissue-based diseases. Here, we provide updated overview heterogeneity function across tissues disease states. We discuss mechanisms cell–mediated protection their potential contributions to autoimmune disorders. Finally, examine how responses might be durably boosted or dampened gain.

Language: Английский

Citations

25
Design and regulation of engineered bacteria for environmental release DOI
Yonatan Chemla, Connor J. Sweeney,

Christopher A. Wozniak

et al.

Nature Microbiology, Journal Year: 2025, Volume and Issue: 10(2), P. 281 - 300

Published: Feb. 4, 2025

Language: Английский

Citations

4
Engineered Bacteria for Disease Diagnosis and Treatment Using Synthetic Biology DOI Creative Commons
Kai Jin, Yi Huang, Hailong Che

et al.

Microbial Biotechnology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 1, 2025

Using synthetic biology techniques, bacteria have been engineered to serve as microrobots for diagnosing diseases and delivering treatments. These can be used individually or in combination microbial consortia. The components within these consortia complement each other, enhancing diagnostic accuracy providing synergistic effects that improve treatment efficacy. application of therapies cancer, intestinal diseases, metabolic disorders underscores their significant potential. impact on the host's native microbiota is crucial, microbes modulate interact with environment, influencing outcomes overall health. Despite numerous advancements, challenges remain. include ensuring long-term survival safety bacteria, developing new chassis gene editing techniques non-model strains, minimising potential toxicity, understanding bacterial interactions host microbiota. This mini-review examines current state disease diagnosis treatment, highlighting challenges, future directions this promising field.

Language: Английский

Citations

3
A multi-omics spatial framework for host-microbiome dissection within the intestinal tissue microenvironment DOI Creative Commons
Bokai Zhu, Yunhao Bai, Yao Yu Yeo

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 31, 2025

The intricate interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations intestinal tissue environment. Our ability study these events on systems level is significantly limited by situ approaches capable of generating simultaneous insights from both microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for probing across multiple spatial modalities. We demonstrate MicroCart investigating gut changes murine colitis model, using proteomics, transcriptomics, glycomics. findings reveal global but systematic transformation responses, encompassing tissue-level remodeling epithelial cell state perturbations, bacterial population shifts, localized inflammatory metabolic process alterations during colitis. enables deep investigation interplay with multi-omics.

Language: Английский

Citations

2