Programmable Bacteria with Dynamic Virulence Modulation System for Precision Antitumor Immunity DOI Creative Commons
Leyang Wu, Lin Li,

Liyuan Qiao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

Engineered bacteria-mediated antitumor approaches have been proposed as promising immunotherapies for cancer. However, the off-target bacterial toxicity narrows therapeutic window. Living microbes will benefit from their controllable immunogenicity within tumors safer applications. In this study, a genetically encoded microbial activation strategy is reported that uses tunable and dynamic expression of surface extracellular polysaccharides to improve biocompatibility while retaining efficacy. Based on screening genes associated with Salmonella survival in macrophages, novel attenuated chassis strain AIS (htrA gene-deficient) highly enriched after administration rapidly cleared normal organs are reported. Subsequently, an engineered strain, AISI-H, constructed based optimized quorum-sensing regulatory system. The AISI-H can achieve recovery tumor-specific virulence through HTRA-RCSA axis-based synthetic gene circuit-mediated increase polysaccharide content. These strains act "off" avoid unwanted immune "on" precise tumor suppression mice. shows significant inhibition potent anticancer immunity melanoma mouse model. exhibits excellent biocompatibility. This regulation expands applications microbe-based therapeutics.

Language: Английский

Probiotic-guided CAR-T cells for solid tumor targeting DOI
Rosa L. Vincent, Candice R. Gurbatri, Fangda Li

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6667), P. 211 - 218

Published: Oct. 12, 2023

A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)-T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species bacteria selectively colonize immune-privileged tumor cores can be engineered antigen-independent platforms for therapeutic delivery. To bridge these approaches, we developed a platform probiotic-guided CAR-T (ProCARs), in which tumor-colonizing probiotics release synthetic label tissue CAR-mediated lysis situ. This system demonstrated cell activation antigen-agnostic was safe effective multiple xenograft syngeneic models human mouse cancers. We further multifunctional co-release chemokines to enhance recruitment response.

Language: Английский

Citations

112

Targeting cytokine and chemokine signaling pathways for cancer therapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

Citations

60

Bioengineering of bacteria for cancer immunotherapy DOI Creative Commons
Dinh-Huy Nguyen, Ari Chong, Yeongjin Hong

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 15, 2023

Here, we provide a brief overview of the approaches and strategies underlying bacteria-based cancer immunotherapy (BCiT). We also describe summarize research in field synthetic biology, which aims to regulate bacterial growth gene expression for immunotherapeutic use. Finally, discuss current clinical status limitations BCiT.

Language: Английский

Citations

59

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

53

Nanozyme‐Coated Bacteria Hitchhike on CD11b+ Immune Cells to Boost Tumor Radioimmunotherapy DOI

Hanghang Li,

Pei Pei, Qing‐Yu He

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Nov. 7, 2023

Bacterial-based delivery strategies have recently emerged as a unique research direction in the field of drug delivery. However, bacterial vectors are quickly phagocytosed by immune cells after entering bloodstream. Taking advantage this phenomenon, herein, work seeks to harness potential micron-sized vectors, and find that inactivated can accumulate at tumor-site intravenous injection through CD11b

Language: Английский

Citations

24

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

Engineered bacteria in tumor immunotherapy DOI
Hua Chen,

Yinrui Zhu,

Chonghai Zhang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 589, P. 216817 - 216817

Published: March 15, 2024

Language: Английский

Citations

11

Sonocatalytic oncolysis microbiota curb intrinsic microbiota lactate metabolism and blockade CD24-Siglec10 immune escape to revitalize immunological surveillance DOI

Xiulin Dong,

Hui Liu, Chao Fang

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122662 - 122662

Published: June 12, 2024

Language: Английский

Citations

11

T cell cascade regulation initiates systemic antitumor immunity through living drug factory of anti-PD-1/IL-12 engineered probiotics DOI Creative Commons
Jian‐Hong Liao, Hong Pan, Guojun Huang

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114086 - 114086

Published: April 1, 2024

Immune checkpoint blockade (ICB) has revolutionized cancer therapy but only works in a subset of patients due to the insufficient infiltration, persistent exhaustion, and inactivation T cells within tumor. Herein, we develop an engineered probiotic (interleukin [IL]-12 nanoparticle Escherichia coli Nissle 1917 [INP-EcN]) acting as living drug factory biosynthesize anti-PD-1 release IL-12 for initiating systemic antitumor immunity through cell cascade regulation. Mechanistically, INP-EcN not continuously biosynthesizes relieving immunosuppression also effectively promote activation, proliferation, infiltration via responsive IL-12, thus reaching sufficient activation threshold ICB. Tumor targeting colonization INP-EcNs dramatically increase local accumulations, significantly inhibiting tumor growth metastasis compared commercial inhibitors. Furthermore, immune profiling reveals that anti-PD-1/IL-12 efficiently effects CD8

Language: Английский

Citations

10

Nano/genetically engineered cells for immunotherapy DOI Creative Commons

Jingrui Shen,

Yang Zhou, Lichen Yin

et al.

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

Published: July 17, 2024

Abstract Immunotherapy has recently emerged as a promising therapeutic modality for the treatment of various diseases such cancer, inflammation, autoimmune diseases, and infectious diseases. Despite its potential, immunotherapy faces challenges related to delivery efficiency off‐target toxicity immunotherapeutic drugs. Nano drug systems offer improvements in biodistribution release kinetics but still suffer from shortcomings high immunogenicity, poor penetration across biological barriers, insufficient tissue permeability. Targeted drugs using living cells become an emerging strategy that can take advantage inherent characteristics deal with defects nano systems. Furthermore, themselves be genetically engineered into cellular enhanced immunotherapy. This review provides in‐depth exploration cell‐derived carriers, detailing their properties, functions, commonly used loading strategies. In addition, role modified synergistic effects are also introduced. By summarizing main advancements limitations field, this offers insights potential cell‐based address existing The introduction recent developments evaluation ongoing research will pave way optimization widespread adoption nano/genetically

Language: Английский

Citations

10