Bacteriophage‐mediated therapy of chondrosarcoma by selective delivery of the tumor necrosis factor alpha (TNFα) gene

Chongchai, Aitthiphon; Waramit, Sajee; Suwan, Keittisak; Al-Bahrani, Mariam; Udomruk, Sasimol; Phitak, Thanyaluck; Kongtawelert, Prachya; Pothacharoen, Peraphan; Hajitou, Amin

doi:10.1096/fj.202002539r

Cited by 12 publications

(16 citation statements)

References 44 publications

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“…Most research on phages in SEA consists of genetic studies, including genomic characterization of phages and bioengineering applications, such as phage typing and phage display. In terms of bioengineering phages for therapeutic applications, SEA scientists reported the use of phages for targeted gene therapy (Namdee et al, 2018;Przystal et al, 2019;Chongchai et al, 2021) and adaptation of nanomaterial-based phage delivery systems (Adamu Ahmad et al, 2016;Kaikabo et al, 2017). There is also a notable amount of research on in vitro testing of phages, including the testing for the phage's host range, biocontrol assays against pathogens, and phage formulation techniques.…”

Section: Phage Research In Seamentioning

confidence: 99%

“…DotBio, a start-up biotechnology company in Singapore, utilizes the phage display technique to produce DotBody technology proposed to be used in multi-functional therapies (https://www.dotbio.com/en/ technology, accessed 20 December 2021). Meanwhile, scientists from SEA reported bioengineered phages with applications as vectors for selective delivery of transgenes in mammalian cells via phage surface modification (Namdee et al, 2018;Chongchai et al, 2021) and dual tumor targeting by hybridization of an adeno-associated virus with the phage capsid (Przystal et al, 2019). However, no specific modifications have been done to create phages specifically targeting clinically relevant bacteria.…”

Section: Phase Two: Laboratory-and Clinic-based Phage Therapy Applicationsmentioning

confidence: 99%

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Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia

Carascal

Cruz-Papa

Remenyi³

et al. 2022

Front. Microbiol.

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Southeast Asia (SEA) can be considered a hotspot of antimicrobial resistance (AMR) worldwide. As recent surveillance efforts in the region reported the emergence of multidrug-resistant (MDR) pathogens, the pursuit of therapeutic alternatives against AMR becomes a matter of utmost importance. Phage therapy, or the use of bacterial viruses called bacteriophages to kill bacterial pathogens, is among the standout therapeutic prospects. This narrative review highlights the current understanding of phages and strategies for a phage revolution in SEA. We define phage revolution as the radical use of phage therapy in infectious disease treatment against MDR infections, considering the scientific and regulatory standpoints of the region. We present a three-phase strategy to encourage a phage revolution in the SEA clinical setting, which involves: (1) enhancing phage discovery and characterization efforts, (2) creating and implementing laboratory protocols and clinical guidelines for the evaluation of phage activity, and (3) adapting regulatory standards for therapeutic phage formulations. We hope that this review will open avenues for scientific and policy-based discussions on phage therapy in SEA and eventually lead the way to its fullest potential in countering the threat of MDR pathogens in the region and worldwide.

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Section: Phage Research In Seamentioning

confidence: 99%

Section: Phase Two: Laboratory-and Clinic-based Phage Therapy Applicationsmentioning

confidence: 99%

Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia

Carascal

Cruz-Papa

Remenyi³

et al. 2022

Front. Microbiol.

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“…Notably, recent studies have shown that the functionalization of TNF-bearing gold nanoparticles with NGR- or isoDGR-containing ligands can enable also the “active” targeted delivery of extremely low, but pharmacologically active, doses of nanodrug (e.g., equivalent to 5 pg of biologically active TNF/mouse) to the tumor vasculature in murine models [ 64 , 86 ]. Finally, genetically modified viruses, bacteria, and bacteriophages, engineered to express TNF alone or in combination with other cytokines, have also been developed [ 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. For example, a recent study performed in a murine model of human glioblastoma have shown that an RGD4C-directed hybrid virus of adeno-associated virus and phage (AAVP) can deliver the TNF gene to the tumors, and induce damage of tumor-associated neovessels and cell death [ 94 ].…”

Section: Clinical Studies With Ngr-tnfmentioning

confidence: 99%

Targeting the Blood–Brain Tumor Barrier with Tumor Necrosis Factor-α

et al. 2022

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The blood–brain tumor barrier represents a major obstacle for anticancer drug delivery to brain tumors. Thus, novel strategies aimed at targeting and breaching this structure are of great experimental and clinical interest. This review is primarily focused on the development and use of a derivative of tumor necrosis factor-α (TNF) that can target and alter the blood–brain-tumor-barrier. This drug, called NGR-TNF, consists of a TNF molecule fused to the Cys-Asn-Gly-Arg-Cys-Gly (CNGRCG) peptide (called NGR), a ligand of aminopeptidase N (CD13)-positive tumor blood vessels. Results of preclinical studies suggest that this peptide-cytokine fusion product represents a valuable strategy for delivering TNF to tumor vessels in an amount sufficient to break the biological barriers that restrict drug penetration in cancer lesions. Moreover, clinical studies performed in patients with primary central nervous system lymphoma, have shown that an extremely low dose of NGR-TNF (0.8 µg/m2) is sufficient to promote selective blood–brain-tumor-barrier alteration, increase the efficacy of R-CHOP (a chemo-immunotherapy regimen) and improve patient survival. Besides reviewing these findings, we discuss the potential problems related to the instability and molecular heterogeneity of NGR-TNF and review the various approaches so far developed to obtain more robust and homogeneous TNF derivatives, as well as the pharmacological properties of other peptide/antibody-TNF fusion products, muteins and nanoparticles that are potentially useful for targeting the blood–brain tumor barrier. Compared to other TNF-related drugs, the administration of extremely low-doses of NGR-TNF or its derivatives appear as promising non-immunogenic approaches to overcome TNF counter-regulatory mechanism and systemic toxicity, thereby enabling safe breaking of the BBTB.

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“…When chondrosarcoma SW1353 cells were exposed to the phage vector encoding a TNFα transgene, distinct targeted cell killing concomitant with the high expression of TNFα and apoptosis-related genes was witnessed. In vivo, chondrosarcoma implant-carrying mice exhibited inhibition of tumor growth post phage vector administration ( Figure 3 ) [ 108 ]. In another study, phage mediated gene replacement therapy was attempted.…”

Section: Using Phages To Target and Regulate Tumor And Its Microenvironmentmentioning

confidence: 99%

Bacteriophages as Solid Tumor Theragnostic Agents

Veeranarayanan

Azam

Kiga

et al. 2021

IJMS

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Cancer, especially the solid tumor sub-set, poses considerable challenges to modern medicine owing to the unique physiological characteristics and substantial variations in each tumor’s microenvironmental niche fingerprints. Though there are many treatment methods available to treat solid tumors, still a considerable loss of life happens, due to the limitation of treatment options and the outcomes of ineffective treatments. Cancer cells evolve with chemo- or radiation-treatment strategies and later show adaptive behavior, leading to failed treatment. These challenges demand tailored and individually apt personalized treatment methods. Bacteriophages (or phages) and phage-based theragnostic vectors are gaining attention in the field of modern cancer medicine, beyond their bactericidal ability. With the invention of the latest techniques to fine-tune phages, such as in the field of genetic engineering, synthetic assembly methods, phage display, and chemical modifications, noteworthy progress in phage vector research for safe cancer application has been realized, including use in pre-clinical studies. Herein, we discuss the distinct fingerprints of solid tumor physiology and the potential for bacteriophage vectors to exploit specific tumor features for improvised tumor theragnostic applications.

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Bacteriophage‐mediated therapy of chondrosarcoma by selective delivery of the tumor necrosis factor alpha (TNFα) gene

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 12 publications

References 44 publications

Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia

Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia

Targeting the Blood–Brain Tumor Barrier with Tumor Necrosis Factor-α

Bacteriophages as Solid Tumor Theragnostic Agents

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