Modified bacterial outer membrane vesicles induce autoantibodies for tumor therapy

Huang, Weiwei; Shu, Congyan; Hua, Liangqun; Zhao, Yilin; Xie, Hanghang; Qi, Jialong; Gao, Feng; Gao, Ruiyu; Chen, Yongjun; Zhang, Qishu; Li, Weiran; Yuan, Mingcui; Ye, Chao; Ma, Yanbing

doi:10.1016/j.actbio.2020.03.030

Cited by 63 publications

(42 citation statements)

References 56 publications

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“…Combination of photodynamic therapy, photothermal, and immunotherapy [ 124 ] BFGF TC-I and B16FIO tumors Used as a cancer vaccine. Induction of antibody production targeting tumor angiogenesis [ 125 ] Protoplast-derived nanovesicles from E. coli Doxorubicin Human lung carcinoma A459 cells Bioengineered with high expression of the epidermal growth factor to target the tumor. Alleviation of systemic toxicity of the chemotherapeutic agent [ 126 ] DMV from E. coli Doxorubicin B16F10 tumor Bioengineered with high expression of RGD motifs to target the tumor.…”

Section: Different Therapeutic Payloads Delivered By Engineered Bacteriamentioning

confidence: 99%

Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Allemailem¹

2021

IJN

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Conventional therapies for cancer eradication like surgery, radiotherapy, and chemotherapy, even though most widely used, still suffer from some disappointing outcomes. The limitations of these therapies during cancer recurrence and metastasis demonstrate the need for better alternatives. Some bacteria preferentially colonize and proliferate inside tumor mass; thus these bacteria can be used as ideal candidates to deliver antitumor therapeutic agents. The bacteria like Bacillus spp., Clostridium spp., E. coli, Listeria spp., and Salmonella spp. can be reprogrammed to produce, transport, and deliver anticancer agents, eg, cytotoxic agents, prodrug converting enzymes, immunomodulators, tumor stroma targeting agents, siRNA, and drug-loaded nanoformulations based on clinical requirements. In addition, these bacteria can be genetically modified to express various functional proteins and targeting ligands that can enhance the targeting approach and controlled drug-delivery. Low tumor-targeting and weak penetration power deep inside the tumor mass limits the use of anticancer drug-nanoformulations. By using anticancer drug nanoformulations and other therapeutic payloads in combination with antitumor bacteria, it makes a synergistic effect against cancer by overcoming the individual limitations. The tumor-targeting bacteria can be either used as a monotherapy or in addition with other anticancer therapies like photothermal therapy, photodynamic therapy, and magnetic field therapy to accomplish better clinical outcomes. The toxicity issues on normal tissues is the main concern regarding the use of engineered antitumor bacteria, which requires deeper research. In this article, the mechanism by which bacteria sense tumor microenvironment, role of some anticancer agents, and the recent advancement of engineering bacteria with different therapeutic payloads to combat cancers has been reviewed. In addition, future prospective and some clinical trials are also discussed.

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Section: Different Therapeutic Payloads Delivered By Engineered Bacteriamentioning

confidence: 99%

Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Allemailem¹

2021

IJN

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“…Genetic modification technology was also applied to E. coli DH5α to assemble MVs surface with murine fibroblast growth factor (FGF). The persistent autoantibodies against FGF could be stimulated in mice after three subcutaneous injections of the engineered MVs, and the growth and metastasis of TC-1 and B16F10 xenograft tumors were effectively inhibited in mice vaccinated with MVs (Huang et al, 2020). Overall, these studies above demonstrate that bacterial MVs can provide targeted loading and delivery of a range of anti-tumor drugs in a highly effective way.…”

Section: Anti-tumor Drug Deliverymentioning

confidence: 70%

“…Firstly, bacterial MVs have a large antitumor drug loading space like synthetic nanoparticles. The protein drugs such as fibroblast growth factors were presented on the surface of MVs (Huang et al, 2020), while siRNA drugs were loaded into MV lumen by electroporation (Gujrati et al, 2014). Secondly, nano-sized MVs are more rigid and they present less leakage during host circulation than traditional liposomes.…”

Section: Anti-tumor Drug Deliverymentioning

confidence: 99%

“…Bacterial MVs have been widely used to deliver different kinds of anti-tumor drugs, including chemo-therapeutic agents, thermo-therapeutic molecules, and immuno-stimulatory elements (Liu et al, 2013;Chen Q. et al, 2020;Huang et al, 2020). A clinic trial has revealed that paclitaxel-loaded bacterial MVs were safe in patients carrying solid tumors and exhibited a modest clinical treatment efficacy (Solomon et al, 2015).…”

Section: Anti-tumor Drug Deliverymentioning

confidence: 99%

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Engineered Remolding and Application of Bacterial Membrane Vesicles

Rao

Zhu

et al. 2021

Front. Microbiol.

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Bacterial membrane vesicles (MVs) are produced by both Gram-positive and Gram-negative bacteria during growth in vitro and in vivo. MVs are nanoscale vesicular structures with diameters ranging from 20 to 400 nm. MVs incorporate bacterial lipids, proteins, and often nucleic acids, and can effectively stimulate host immune response against bacterial infections. As vaccine candidates and drug delivery systems, MVs possess high biosafety owing to the lack of self-replication ability. However, wild-type bacterial strains have poor MV yield, and MVs from the wild-type strains may be harmful due to the carriage of toxic components, such as lipopolysaccharides, hemolysins, enzymes, etc. In this review, we summarize the genetic modification of vesicle-producing bacteria to reduce MV toxicity, enhance vesicle immunogenicity, and increase vesicle production. The engineered MVs exhibit broad applications in vaccine designs, vaccine delivery vesicles, and drug delivery systems.

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“… 88 Recently, genetic engineering MVs could exhibit exogenous antigen protein, provoke antigen-specific immune response and combat tumor, such as ovalbumin fragment 100 and basic fibroblast growth factor. 101 The tumor antigen HPV16E7 was embedded on the surface as well as in the lumen of E. coli -derived MVs through the location ability of ClyA. 102 This kind of strategy provided a novel vaccine delivery vector, which could be used to deliver more neoantigens to induce specific antitumor immune response effectively.…”

Section: Bacteria-derived Outer Membrane Based Nanoplatformsmentioning

confidence: 99%

Nanotechnology-Employed Bacteria-Based Delivery Strategy for Enhanced Anticancer Therapy

Ye¹,

Liu²,

Lu³

et al. 2021

IJN

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Bacteria and their derivatives (membrane vesicles, MVs) exhibit great advantages for targeting hypoxic tumor cores, strong penetration ability and activating immune responses, holding great potential as auspicious candidates for therapeutic and drug-delivery applications. However, the safety issues and low therapeutic efficiency by single administration still need to be solved. To further optimize their performance and to utilize their natural abilities, scientists have strived to modify bacteria with new moieties on their surface while preserving their advantages. The aim of this review is to give a comprehensive overview of a non-genetic engineering modification strategy that can be used to optimize the bacteria with nanomaterials and the design strategy that can be used to optimize MVs for better targeted therapy. Here, the advantages and disadvantages of these processes and their applicability for the development of bacteria-related delivery system as antitumor therapeutic agents are discussed. The prospect and the challenges of the above targeted delivery system are also proposed.

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Modified bacterial outer membrane vesicles induce autoantibodies for tumor therapy

Cited by 63 publications

References 56 publications

Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Engineered Remolding and Application of Bacterial Membrane Vesicles

Nanotechnology-Employed Bacteria-Based Delivery Strategy for Enhanced Anticancer Therapy

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