Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefo...Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefore,robust immune system activation is crucial to enhance the efficacy of cancer immunotherapy in clinical applications.Bacteria have shown the ability to target the hypoxic TMEs while activating both innate and adaptive immune responses.Engineered bacteria,modified through chemical or biological methods,can be endowed with specific physiological properties,such as diverse surface antigens,metabolites,and improved biocompatibility.These unique characteristics give engineered bacteria distinct advantages in stimulating anti-cancer immune responses.This review explores the potential regulatory mechanisms of engineered bacteria in modulating both innate and adaptive immunity while also forecasting the future development and challenges of using engineered bacteria in clinical cancer immunotherapy.展开更多
In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless re...In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless revealed a tantalizing truth:The immune system,when properly provoked,could attack cancer.Over a century later,researchers have transformed this observation into a precision strike force.展开更多
In Rhodopseudomonas palustris,an arsM gene,encoding bacterial and archaeal homologues of the mammalian Cyt19 As（III） S-adenosylmethionine methytransferase,was regulated by arsenicals.An expression of arsM was introd...In Rhodopseudomonas palustris,an arsM gene,encoding bacterial and archaeal homologues of the mammalian Cyt19 As（III） S-adenosylmethionine methytransferase,was regulated by arsenicals.An expression of arsM was introduced into strains for the methylation of arsenic.When arsM was expressed in Sphingomonas desiccabilis and Bacillus idriensis,it had 10 folds increase of methyled arsenic gas compared to wild type in aqueous system.In soil system,about 2.2%–4.5% of arsenic was removed by biovolatilization during 30 days.This study demonstrated that arsenic could be removed through volatilization from the contaminated soil by bacteria which have arsM gene expressed.These results showed that it is possible to use microorganisms expressing arsM as an inexpensive,efficient strategy for arsenic bioremediation from contaminated water and soil.展开更多
Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biolog...Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biological IR detection methods are deficient.Here,a living composite hydrogel consisting of engineered bacteria and gelatin/sodium alginate was 3D-printed for the biological detection of IR.Three strains of PrecA::egfp gene circuit-containing engineered Escherichia coli were constructed with IR-dependent fluorescence,and the DH5αstrain was finally selected due to its highest radiation response and fluorescence.Engineered bacteria were loaded in a series of gelatin/sodium alginate matrix hydrogels with different rheology,3D printability and bacterial applicability.A high-gelatin-content hydrogel containing 10%gelatin/1.25%sodium alginatewas optimal.The optimal living composite hydrogelwas 3D-printedwith the special bioink,which reported significant green fluorescence underγ-ray radiation.The living composite hydrogel provides a biological strategy for the detection of environmental ionizing radiation.展开更多
With the development of dyeing wastewater treatment biotechnology, the advantages of bioaugmentation bacteria gradually catch people’s eyes. Therefore, its construction and application research has also attracted the...With the development of dyeing wastewater treatment biotechnology, the advantages of bioaugmentation bacteria gradually catch people’s eyes. Therefore, its construction and application research has also attracted the attention of the majority of scholars. This article summaries the construction and application of bioaugmentation engineered bacteria used to treat dyeing wastewater in recent years, including the screening, domestication and application of single and mixed flora bacteria. In addition, the impact of the strengthening effect of all genes is also described in this paper. Finally, the optimization and promoted use of bioaugmentation bacteria are out looked.展开更多
For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,clas...For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,classified as anaerobic,aquatic,and gram-negative microorganisms,exhibit remarkable motility and precise control over their internal biomineralization processes.This unique ability results in the formation of magnetic nanoparticles arranged along filamentous structures in a catenary fashion,enclosed within a membrane.These bacteria possess distinctive biochemical properties that facilitate their precise positioning within complex environments.By harnessing these biochemical attributes,MTB could potentially offer substantial advantages in the realm of cancer therapy.This article reviews the drug delivery capabilities of MTB in tumor treatment and explores various applications based on their inherent properties.The objective is to provide a comprehensive understanding of MTB-driven drug delivery and stimulate innovative insights in this field.展开更多
A mixed bacterial flora was isolated from the soil of two petroleum-contaminated sites, then cultivated and domesticated in an open environment. The bacteria were used to degrade engine oil in wastewater. The optimum ...A mixed bacterial flora was isolated from the soil of two petroleum-contaminated sites, then cultivated and domesticated in an open environment. The bacteria were used to degrade engine oil in wastewater. The optimum biodegradation conditions for all engine oil concentrations of respectively 489 mg L^-1, 1. 075 mg L^-1 and 2 088 mg L^-1 are bacterial inoculum concentration of 0.1%, temperature at 30 ℃ to 35 ℃, pH 7.0 to 7.5, and rotation at 190 r mia^-1 to 240 r rain^-1. The second-order kinetic model proposed by Quiroga and Sales describes the characteristics of the biodegradation of the engine oil very well. Engine oil concentration barely changes the growth rate of the bacterial consortium. The mixed bacterial flora has a high biodegrading capability for engine oil.展开更多
Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance be...Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance between safety and immunogenicity.Genetically engineered bacteria with virulence factors removed could further enhance antitumor ability by integrating genetic elements.In addition,bacterial derivatives,including outer membrane vesicles(OMVs)produced by bacterial secretion and nanovesicles synthesized by modification of OMVs,could enhance antitumor immunity while improving safety.This perspective discusses the unique advantages of engineered bacteria and their derivatives for immunotherapy,as well as the challenges that need to be overcome to achieve clinical translation.展开更多
Chinese scientists have recently exploited a new strategy to enhance peptides’activity against Gram-negative bacteria effectively by conjugating the peptides onto a rod-like virus.The work,published online inNano Let...Chinese scientists have recently exploited a new strategy to enhance peptides’activity against Gram-negative bacteria effectively by conjugating the peptides onto a rod-like virus.The work,published online inNano Letters,was directed by Prof.NIU Zhongwei and Associate Prof.TIAN Ye from the Technical Institute of Physics and Chemistry(TIPC)of the Chinese Academy of Sciences(CAS).展开更多
Lactic acid bacteria(LAB)exopolysaccharides(EPS)reveal high safety and multiple activities,and are typical postbiotics produced by LAB during fermentation.In this paper,6583 articles on LAB-EPS from Web of Science and...Lactic acid bacteria(LAB)exopolysaccharides(EPS)reveal high safety and multiple activities,and are typical postbiotics produced by LAB during fermentation.In this paper,6583 articles on LAB-EPS from Web of Science and Elsevier databases were retrieved,and 236 articles related to this review were screened.The EPS from 90 LAB strains were summarized in terms of their extraction methods,yield,molecular weight,monosaccharide composition,glycosidic bond configuration and the structural and activity relationships(SARs).However,there exist great challenges as for the low yield and high cost in EPS production.Therefore,this review further elaborated the mechanism of EPS secretion,the anabolic pathway of EPS,the structure and mechanism of key enzymes involving in EPS synthesis process,the prospect of gene regulation for EPS secretion,and proposed the engineering strategies for increasing EPS yield or tailored EPS design in recent years.In addition,CRISPR/Cas9 gene editing technology was also discussed in the production control of EPS in LAB.Finally,the engineering strategy of increasing EPS yield in recent years was proposed.This work might provide important theoretical support for the production and application of LAB-based EPS.展开更多
Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platf...Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platform,the engineered bacterial therapeutics demonstrate exceptional targeting precision and favorable safety profiles.Through attenuation and programmable control strategies,these systems enable highly specific drug delivery,showing significant therapeutic potential in oncology and inflammatory bowel disease(IBD).展开更多
Recent advancements in cancer therapeutics,including targeted therapies and immunotherapies,have significantly improved treatment outcomes but remain limited by challenges such as off-target toxicity,poor penetration ...Recent advancements in cancer therapeutics,including targeted therapies and immunotherapies,have significantly improved treatment outcomes but remain limited by challenges such as off-target toxicity,poor penetration into deep tumor tissues,and the emergence of drug resistance.Engineered bacteria-based cancer therapies present a novel and versatile approach to address these limitations.Leveraging their ability to selectively colonize tumor microenvironments,bacteria can elicit antitumor immune responses and serve as platforms for the localized delivery of therapeutic agents.Through genetic engineering and synthetic biology,bacteria can be programmed to produce anticancer payloads tailored to clinical needs.This review highlights recent progress in the design and application of engineered bacteria for cancer therapy,emphasizing innovative strategies to enhance therapeutic delivery and efficacy.In addition,we discuss the integration of bacteria-based approaches with conventional therapies to overcome intratumor heterogeneity and improve treatment outcomes.Finally,we discuss insights from past and ongoing clinical trials of tumor-targeting bacteria,alongside challenges that must be surmounted to realize their full therapeutic promise.展开更多
Cancer therapy remains a critical medical challenge.Immunotherapy is an emerging approach to regulating the immune system to fight cancer and has shown therapeutic potential.Due to their immunogenicity,bacteria have b...Cancer therapy remains a critical medical challenge.Immunotherapy is an emerging approach to regulating the immune system to fight cancer and has shown therapeutic potential.Due to their immunogenicity,bacteria have been developed as drug-delivery vehicles in cancer immunotherapy.However,ensuring the safety and efficacy of this approach poses a considerable challenge.This paper comprehensively explains the fundamental processes and synthesis principles involved in immunotherapy utilizing engineered bacteria.Initially,we list common engineered strains and discuss that growth control through genetic mutation promises therapeutic safety.By considering the characteristics of the tumor microenvironment and the interaction of specific molecules,the precision targeting of tumors can be improved.Furthermore,we present a foundational paradigm for genetic circuit construction to achieve controlled gene activation and logical expression,directly determining drug synthesis and release.Finally,we review the immunogenicity,the expression of immunomodulatory factors,the delivery of immune checkpoint inhibitors,and the utilization of bacteria as tumor vaccines to stimulate the immune system and facilitate the efficacy of cancer immunotherapy.展开更多
The unique physiological characteristics and complexity of tumor,in addition to drug resistance result in traditional therapies,such as chemotherapy and radiotherapy,being unable to achieve complete elimination of can...The unique physiological characteristics and complexity of tumor,in addition to drug resistance result in traditional therapies,such as chemotherapy and radiotherapy,being unable to achieve complete elimination of cancer cells.Meanwhile,the emerging immunotherapy suffers from a low patient response rate.Bacterial therapies are highly targeted.Bacteria can penetrate deep into the tumor and show good tumor inhibition.However,natural bacteria have the limitation of high toxicity and inability to meet the demand for efficient therapeutics.Recent advances in synthetic biology and materials science relate to the safety and efficacy of bacterial therapeutics,promising to develop engineered bacteria with low toxicity and complex therapeutic functions.Engineered bacteria that express anticancer drug molecules can target the tumor region,synthesizing and releasing payloads in response to internal and external stimuli.This process leads to the regression of the tumor and the effective inhibition of recurrence.This review outlines the recent advancements in the field of engineered bacteria research,particularly focusing on their applications in anti-tumor therapy.It also includes the advantageous features and mechanisms of engineered bacteria therapy,synthetic biology modification methods,and future challenges and directions of engineered bacteria therapy.展开更多
Adoptive cell therapy with chimeric antigen receptor(CAR)immunotherapy has demonstrated remarkable potential for hematologic malignancy while encountering challenges in extending the responsive list to solid tumors.Th...Adoptive cell therapy with chimeric antigen receptor(CAR)immunotherapy has demonstrated remarkable potential for hematologic malignancy while encountering challenges in extending the responsive list to solid tumors.The major hurdles include a lack of tumor-specific targets,inefficient trafficking,and tumor infiltration of the immune effector cells,along with their dysfunction and exhaustion in immune-suppressive tumor microenvironment(TME)1.Bacteria-mediated cancer immunotherapies(BCITs)have made remarkable progress in cancer immunotherapy over the past two decades.展开更多
After a century of standstill,bacteria-based tumor therapy has resurged recently benefiting from the revolution of tumor immunotherapy,which provides unique solutions to tackle the obstacles of traditional tumor treat...After a century of standstill,bacteria-based tumor therapy has resurged recently benefiting from the revolution of tumor immunotherapy,which provides unique solutions to tackle the obstacles of traditional tumor treatments.Obligate and facultative anaerobes with active tropism can selectively colonize at tumor sites and suppress tumor growth via different mechanisms,serving as attractive tools for tumor treatment either as a monotherapy or combining with other therapies for synergistic anti-tumor effects.In this critical review,we introduce the recent advances of bacteria-based tumor therapy from the following aspects.First,the general properties of bacteria are reviewed emphasizing on their structural components related to tumor immunotherapy,and the main bacteria that have been used in tumor therapy are listed.Then,the benefits of bacteria for tumor therapy are illustrated,such as tumor targetability,deep penetration,and facile genetic engineering for attenuation,enhanced efficacy,as well as bioimaging.Next,anti-tumor mechanisms of bacteria are summarized,which refer to intrinsic tumoricidal activities,immune activation,bacteria metabolism,and their capability to regulate gut microbiota homeostasis.Moreover,bacteria could act as carriers to deliver various types of therapeutics to achieve combination therapy with improved efficacy.In addition,several challenges for anti-tumor applications of bacteria are discussed regarding the delivery,efficacy and safety issues,and potential solutions are also provided.Finally,the possible improvements and perspectives are discussed in the end,which provide a guideline for the design of advanced bacteria-based tumor therapeutics in the future.展开更多
基金supported by the Science and Technology Research Project of Jilin Education Bureau(No.JJKH20230804KJ)。
文摘Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefore,robust immune system activation is crucial to enhance the efficacy of cancer immunotherapy in clinical applications.Bacteria have shown the ability to target the hypoxic TMEs while activating both innate and adaptive immune responses.Engineered bacteria,modified through chemical or biological methods,can be endowed with specific physiological properties,such as diverse surface antigens,metabolites,and improved biocompatibility.These unique characteristics give engineered bacteria distinct advantages in stimulating anti-cancer immune responses.This review explores the potential regulatory mechanisms of engineered bacteria in modulating both innate and adaptive immunity while also forecasting the future development and challenges of using engineered bacteria in clinical cancer immunotherapy.
文摘In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless revealed a tantalizing truth:The immune system,when properly provoked,could attack cancer.Over a century later,researchers have transformed this observation into a precision strike force.
基金supported by the National Natural Science Foundation of China (No.40973058)the Ministry of Science and Technology (No.2007CB407304)
文摘In Rhodopseudomonas palustris,an arsM gene,encoding bacterial and archaeal homologues of the mammalian Cyt19 As（III） S-adenosylmethionine methytransferase,was regulated by arsenicals.An expression of arsM was introduced into strains for the methylation of arsenic.When arsM was expressed in Sphingomonas desiccabilis and Bacillus idriensis,it had 10 folds increase of methyled arsenic gas compared to wild type in aqueous system.In soil system,about 2.2%–4.5% of arsenic was removed by biovolatilization during 30 days.This study demonstrated that arsenic could be removed through volatilization from the contaminated soil by bacteria which have arsM gene expressed.These results showed that it is possible to use microorganisms expressing arsM as an inexpensive,efficient strategy for arsenic bioremediation from contaminated water and soil.
基金supported by the Special Program for Capability Promotion
文摘Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biological IR detection methods are deficient.Here,a living composite hydrogel consisting of engineered bacteria and gelatin/sodium alginate was 3D-printed for the biological detection of IR.Three strains of PrecA::egfp gene circuit-containing engineered Escherichia coli were constructed with IR-dependent fluorescence,and the DH5αstrain was finally selected due to its highest radiation response and fluorescence.Engineered bacteria were loaded in a series of gelatin/sodium alginate matrix hydrogels with different rheology,3D printability and bacterial applicability.A high-gelatin-content hydrogel containing 10%gelatin/1.25%sodium alginatewas optimal.The optimal living composite hydrogelwas 3D-printedwith the special bioink,which reported significant green fluorescence underγ-ray radiation.The living composite hydrogel provides a biological strategy for the detection of environmental ionizing radiation.
文摘With the development of dyeing wastewater treatment biotechnology, the advantages of bioaugmentation bacteria gradually catch people’s eyes. Therefore, its construction and application research has also attracted the attention of the majority of scholars. This article summaries the construction and application of bioaugmentation engineered bacteria used to treat dyeing wastewater in recent years, including the screening, domestication and application of single and mixed flora bacteria. In addition, the impact of the strengthening effect of all genes is also described in this paper. Finally, the optimization and promoted use of bioaugmentation bacteria are out looked.
基金supported by the National Natural Science Foundation of China(No.3190110313 to K.Ma)Special Foundation of President of the Chinese Academy of Sciences(No.YZJJ2022QN_(4)4)+2 种基金HFIPS Director’s Fund(Nos.E16CWK123X1YZJJQY202201)the Heye Health Technology Chong Ming Project(No.HYCMP-2022012 to Y.Wang)。
文摘For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,classified as anaerobic,aquatic,and gram-negative microorganisms,exhibit remarkable motility and precise control over their internal biomineralization processes.This unique ability results in the formation of magnetic nanoparticles arranged along filamentous structures in a catenary fashion,enclosed within a membrane.These bacteria possess distinctive biochemical properties that facilitate their precise positioning within complex environments.By harnessing these biochemical attributes,MTB could potentially offer substantial advantages in the realm of cancer therapy.This article reviews the drug delivery capabilities of MTB in tumor treatment and explores various applications based on their inherent properties.The objective is to provide a comprehensive understanding of MTB-driven drug delivery and stimulate innovative insights in this field.
基金Funded by the Natural Science Foundation of China (No.40571145).
文摘A mixed bacterial flora was isolated from the soil of two petroleum-contaminated sites, then cultivated and domesticated in an open environment. The bacteria were used to degrade engine oil in wastewater. The optimum biodegradation conditions for all engine oil concentrations of respectively 489 mg L^-1, 1. 075 mg L^-1 and 2 088 mg L^-1 are bacterial inoculum concentration of 0.1%, temperature at 30 ℃ to 35 ℃, pH 7.0 to 7.5, and rotation at 190 r mia^-1 to 240 r rain^-1. The second-order kinetic model proposed by Quiroga and Sales describes the characteristics of the biodegradation of the engine oil very well. Engine oil concentration barely changes the growth rate of the bacterial consortium. The mixed bacterial flora has a high biodegrading capability for engine oil.
基金supported by the National Natural Science Foundation of China(nos.82222035 and 82372106)the Shenzhen Medical Research Found(no.B2302041).
文摘Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance between safety and immunogenicity.Genetically engineered bacteria with virulence factors removed could further enhance antitumor ability by integrating genetic elements.In addition,bacterial derivatives,including outer membrane vesicles(OMVs)produced by bacterial secretion and nanovesicles synthesized by modification of OMVs,could enhance antitumor immunity while improving safety.This perspective discusses the unique advantages of engineered bacteria and their derivatives for immunotherapy,as well as the challenges that need to be overcome to achieve clinical translation.
基金supported by the National Key R&D Programthe NSFC+2 种基金the YIPA of CASthe Beijing Natural Science Foundationthe Presidential Foundation of TIPC。
文摘Chinese scientists have recently exploited a new strategy to enhance peptides’activity against Gram-negative bacteria effectively by conjugating the peptides onto a rod-like virus.The work,published online inNano Letters,was directed by Prof.NIU Zhongwei and Associate Prof.TIAN Ye from the Technical Institute of Physics and Chemistry(TIPC)of the Chinese Academy of Sciences(CAS).
基金supported by the Natural Science Foundation of Heilongjiang Province(LH2021C075)Basic Research Business Expenses and Research Projects of Provincial Higher Education Institutions in Heilongjiang Province(2022-KYYWF-1077).
文摘Lactic acid bacteria(LAB)exopolysaccharides(EPS)reveal high safety and multiple activities,and are typical postbiotics produced by LAB during fermentation.In this paper,6583 articles on LAB-EPS from Web of Science and Elsevier databases were retrieved,and 236 articles related to this review were screened.The EPS from 90 LAB strains were summarized in terms of their extraction methods,yield,molecular weight,monosaccharide composition,glycosidic bond configuration and the structural and activity relationships(SARs).However,there exist great challenges as for the low yield and high cost in EPS production.Therefore,this review further elaborated the mechanism of EPS secretion,the anabolic pathway of EPS,the structure and mechanism of key enzymes involving in EPS synthesis process,the prospect of gene regulation for EPS secretion,and proposed the engineering strategies for increasing EPS yield or tailored EPS design in recent years.In addition,CRISPR/Cas9 gene editing technology was also discussed in the production control of EPS in LAB.Finally,the engineering strategy of increasing EPS yield in recent years was proposed.This work might provide important theoretical support for the production and application of LAB-based EPS.
基金supported by the Hunan Natural Science Foundation(2023JJ20022).
文摘Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platform,the engineered bacterial therapeutics demonstrate exceptional targeting precision and favorable safety profiles.Through attenuation and programmable control strategies,these systems enable highly specific drug delivery,showing significant therapeutic potential in oncology and inflammatory bowel disease(IBD).
文摘Recent advancements in cancer therapeutics,including targeted therapies and immunotherapies,have significantly improved treatment outcomes but remain limited by challenges such as off-target toxicity,poor penetration into deep tumor tissues,and the emergence of drug resistance.Engineered bacteria-based cancer therapies present a novel and versatile approach to address these limitations.Leveraging their ability to selectively colonize tumor microenvironments,bacteria can elicit antitumor immune responses and serve as platforms for the localized delivery of therapeutic agents.Through genetic engineering and synthetic biology,bacteria can be programmed to produce anticancer payloads tailored to clinical needs.This review highlights recent progress in the design and application of engineered bacteria for cancer therapy,emphasizing innovative strategies to enhance therapeutic delivery and efficacy.In addition,we discuss the integration of bacteria-based approaches with conventional therapies to overcome intratumor heterogeneity and improve treatment outcomes.Finally,we discuss insights from past and ongoing clinical trials of tumor-targeting bacteria,alongside challenges that must be surmounted to realize their full therapeutic promise.
基金supported by National Key Research and Development Program of China(2023YFC3402600)National Natural Science Foundation of China(W2411072 and 82402460)Sanming Project of Medicine in Shenzhen(SZSM202111011).
文摘Cancer therapy remains a critical medical challenge.Immunotherapy is an emerging approach to regulating the immune system to fight cancer and has shown therapeutic potential.Due to their immunogenicity,bacteria have been developed as drug-delivery vehicles in cancer immunotherapy.However,ensuring the safety and efficacy of this approach poses a considerable challenge.This paper comprehensively explains the fundamental processes and synthesis principles involved in immunotherapy utilizing engineered bacteria.Initially,we list common engineered strains and discuss that growth control through genetic mutation promises therapeutic safety.By considering the characteristics of the tumor microenvironment and the interaction of specific molecules,the precision targeting of tumors can be improved.Furthermore,we present a foundational paradigm for genetic circuit construction to achieve controlled gene activation and logical expression,directly determining drug synthesis and release.Finally,we review the immunogenicity,the expression of immunomodulatory factors,the delivery of immune checkpoint inhibitors,and the utilization of bacteria as tumor vaccines to stimulate the immune system and facilitate the efficacy of cancer immunotherapy.
基金the National Natural Science Foundation of China(62375093 and 32422042)Technology Innovation Program of Hubei Province(2024BCB058)。
文摘The unique physiological characteristics and complexity of tumor,in addition to drug resistance result in traditional therapies,such as chemotherapy and radiotherapy,being unable to achieve complete elimination of cancer cells.Meanwhile,the emerging immunotherapy suffers from a low patient response rate.Bacterial therapies are highly targeted.Bacteria can penetrate deep into the tumor and show good tumor inhibition.However,natural bacteria have the limitation of high toxicity and inability to meet the demand for efficient therapeutics.Recent advances in synthetic biology and materials science relate to the safety and efficacy of bacterial therapeutics,promising to develop engineered bacteria with low toxicity and complex therapeutic functions.Engineered bacteria that express anticancer drug molecules can target the tumor region,synthesizing and releasing payloads in response to internal and external stimuli.This process leads to the regression of the tumor and the effective inhibition of recurrence.This review outlines the recent advancements in the field of engineered bacteria research,particularly focusing on their applications in anti-tumor therapy.It also includes the advantageous features and mechanisms of engineered bacteria therapy,synthetic biology modification methods,and future challenges and directions of engineered bacteria therapy.
基金supported by grants from the National Key R&D Program of China(2022YFB3808100 and 2021YFA0909900,Xiao Zhao)the National Natural Science Foundation of China(32222045 and 32171384,Xiao Zhao)High Level Chinese Medical Hospital Promotion Project(HLCMHPP2023001,HLCMHPP2023097,and HLCMHPP2023085,Jie Li).
文摘Adoptive cell therapy with chimeric antigen receptor(CAR)immunotherapy has demonstrated remarkable potential for hematologic malignancy while encountering challenges in extending the responsive list to solid tumors.The major hurdles include a lack of tumor-specific targets,inefficient trafficking,and tumor infiltration of the immune effector cells,along with their dysfunction and exhaustion in immune-suppressive tumor microenvironment(TME)1.Bacteria-mediated cancer immunotherapies(BCITs)have made remarkable progress in cancer immunotherapy over the past two decades.
基金supported by National Natural Science Foundation of China(Nos.U1903125,82071986)Natural Science Foundation of Hunan province in China(No.2021JJ20084)the Science and Technology Innovation Program of Hunan Province(No.2021RC_(3)020).
文摘After a century of standstill,bacteria-based tumor therapy has resurged recently benefiting from the revolution of tumor immunotherapy,which provides unique solutions to tackle the obstacles of traditional tumor treatments.Obligate and facultative anaerobes with active tropism can selectively colonize at tumor sites and suppress tumor growth via different mechanisms,serving as attractive tools for tumor treatment either as a monotherapy or combining with other therapies for synergistic anti-tumor effects.In this critical review,we introduce the recent advances of bacteria-based tumor therapy from the following aspects.First,the general properties of bacteria are reviewed emphasizing on their structural components related to tumor immunotherapy,and the main bacteria that have been used in tumor therapy are listed.Then,the benefits of bacteria for tumor therapy are illustrated,such as tumor targetability,deep penetration,and facile genetic engineering for attenuation,enhanced efficacy,as well as bioimaging.Next,anti-tumor mechanisms of bacteria are summarized,which refer to intrinsic tumoricidal activities,immune activation,bacteria metabolism,and their capability to regulate gut microbiota homeostasis.Moreover,bacteria could act as carriers to deliver various types of therapeutics to achieve combination therapy with improved efficacy.In addition,several challenges for anti-tumor applications of bacteria are discussed regarding the delivery,efficacy and safety issues,and potential solutions are also provided.Finally,the possible improvements and perspectives are discussed in the end,which provide a guideline for the design of advanced bacteria-based tumor therapeutics in the future.
