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

Synthetically programmed antioxidant delivery by a domesticated skin commensal DOI Creative Commons
Guillermo Nevot, Javier Santos‐Moreno, Nil Campamà Sanz

et al.

Cell Systems, Journal Year: 2025, Volume and Issue: 16(2), P. 101169 - 101169

Published: Feb. 1, 2025

Bacteria represent a promising dynamic delivery system for the treatment of disease. In skin, relevant location Cutibacterium acnes within hair follicle makes this bacterium an attractive chassis dermal biotechnological applications. Here, we provide genetic toolbox engineering traditionally intractable bacterium, including basic gene expression tools, biocontainment strategies, markerless engineering, and transcriptional regulation. As proof concept, develop antioxidant-secreting strain capable reducing oxidative stress in UV model.

Language: Английский

Citations

2

Mapping the T cell repertoire to a complex gut bacterial community DOI
Kazuki Nagashima, Aishan Zhao, Katayoon Atabakhsh

et al.

Nature, Journal Year: 2023, Volume and Issue: 621(7977), P. 162 - 170

Published: Aug. 16, 2023

Language: Английский

Citations

40

The human microbiome and cancer: a diagnostic and therapeutic perspective DOI Creative Commons
Shruthi Kandalai, Huapeng Li, Nan Zhang

et al.

Cancer Biology & Therapy, Journal Year: 2023, Volume and Issue: 24(1)

Published: July 27, 2023

Recent evidence has shown that the human microbiome is associated with various diseases, including cancer. The salivary microbiome, fecal and circulating microbial DNA in blood plasma have all been used experimentally as diagnostic biomarkers for many types of microbiomes present within local tissue, other regions, tumors themselves to promote restrict development progression cancer, most often by affecting cancer cells or host immune system. These microbes also impact efficacy therapies, radiation, chemotherapy, immunotherapy. Here, we review research advances focused on how these different facets why they are important clinical care It only better understanding roles play diagnosis, development, progression, treatment will be able catch treat early.

Language: Английский

Citations

38

Melanoma and microbiota: Current understanding and future directions DOI Creative Commons
Bertrand Routy, Tanisha Jackson, Laura Mählmann

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 42(1), P. 16 - 34

Published: Dec. 28, 2023

Over the last decade, composition of gut microbiota has been found to correlate with outcomes cancer patients treated immunotherapy. Accumulating evidence points various mechanisms by which intestinal bacteria act on distal tumors and how harness this complex ecosystem circumvent primary resistance immune checkpoint inhibitors. Here, we review state field in context melanoma, recent breakthroughs defining microbial modes action, modulate enhance response The host-microbe interaction may be deciphered use "omics" technologies, will guide patient stratification development microbiota-centered interventions. Efforts needed advance current gaps knowledge are also discussed.

Language: Английский

Citations

32

Emerging clinical relevance of microbiome in cancer: promising biomarkers and therapeutic targets DOI Creative Commons
Jia‐Hao Dai,

Xi-Rong Tan,

Han Qiao

et al.

Protein & Cell, Journal Year: 2023, Volume and Issue: 15(4), P. 239 - 260

Published: Nov. 8, 2023

Abstract The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years, leading to numerous researches on microbiome entering clinical evaluation. As promising biomarkers therapeutic targets, critical involvement practice increasingly appreciated. Here, recent progress this field is reviewed. We describe potential tumor-associated as effective diagnostic prognostic biomarkers, respectively. In addition, we highlight relationship between efficacy, toxicity, or side effects commonly utilized treatments cancer, including chemotherapy, radiotherapy, immunotherapy. Given that microbial factors treatment outcome, further summarize some dominating interventions discuss hidden risks these strategies. This review aims provide an overview applications advancements microbes relevance.

Language: Английский

Citations

25

Delivery of a sebum modulator by an engineered skin microbe in mice DOI
Nastassia Knödlseder, María-José Fábrega, Javier Santos‐Moreno

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: 42(11), P. 1661 - 1666

Published: Jan. 9, 2024

Language: Английский

Citations

14

Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin DOI
Tianze Yu, Xiaoqiang Xu, Yang Liu

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(7), P. 1129 - 1146.e8

Published: June 26, 2024

Language: Английский

Citations

12

Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments DOI Creative Commons
Lisa Feldman

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 26, 2024

Glioblastoma (GBM) tumors are the most aggressive primary brain in adults that, despite maximum treatment, carry a dismal prognosis. GBM exhibit tissue hypoxia, which promotes tumor aggressiveness and maintenance of glioma stem cells creates an overall immunosuppressive landscape. This article reviews how hypoxic conditions overlap with inflammatory responses, favoring proliferation inhibiting cytotoxic T cell development. Immunotherapies, including vaccines, immune checkpoint inhibitors, CAR-T therapy, represent promising avenues for treatment. However, challenges such as heterogeneity, TME, BBB restrictiveness hinder their effectiveness. Strategies to address these challenges, combination therapies targeting actively being explored improve outcomes patients. Targeting hypoxia immunotherapy represents potential strategy enhance treatment efficacy.

Language: Английский

Citations

12

Discovery and engineering of the antibody response to a prominent skin commensal DOI
Djenet Bousbaine, Katherine D. Bauman, Y. Erin Chen

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Language: Английский

Citations

12

Engineering bacteria for cancer immunotherapy DOI Creative Commons
Jesse G. Zalatan, Lorenzo Petrini, Roger Geiger

et al.

Current Opinion in Biotechnology, Journal Year: 2024, Volume and Issue: 85, P. 103061 - 103061

Published: Jan. 13, 2024

Bacterial therapeutics have emerged as promising delivery systems to target tumors. These engineered live can be harnessed modulate the tumor microenvironment or deliver and selectively release therapeutic payloads A major challenge is bacteria systemically without causing widespread inflammation, which critical for many tumors that are not accessible direct intratumoral injection. We describe potential strategies address this challenge, along with approaches specific payload biocontainment ensure safety. will pave way development of cost-effective, widely applicable next-generation cancer therapeutics.

Language: Английский

Citations

11