A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications

Mett, Vadim; Kurnasov, Oleg V.; Bespalov, Ivan A.; Molodtsov, Ivan; Brackett, Craig M.; Burdelya, Lyudmila; Purmal, Andrei A.; Gleiberman, Anatoli S.; Toshkov, Ilia; Burkhart, Catherine; Kogan, Yakov; Andrianova, Ekaterina L.; Gudkov, Andrei V.; Osterman, Andrei L.

doi:10.1038/s42003-021-01978-6

Cited by 17 publications

(9 citation statements)

References 34 publications

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“…For example, the TLR2 is usually activated by the lipoproteins of Gram-positive bacteria, but it can also be activated by Pam3CSK4 [ 127 , 130 ]. Additionally, the CpG DNA is the natural agonist of TLR21, while the CpG DNA assemblies, synthetic single-stranded DNA, can also possess TLR21 enhancement activity [ 134 , 135 , 136 ].…”

Section: Vaccine Adjuvantsmentioning

confidence: 99%

Advances in Poultry Vaccines: Leveraging Biotechnology for Improving Vaccine Development, Stability, and Delivery

Abdelaziz,

Helmy,

Yitbarek

et al. 2024

Vaccines

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With the rapidly increasing demand for poultry products and the current challenges facing the poultry industry, the application of biotechnology to enhance poultry production has gained growing significance. Biotechnology encompasses all forms of technology that can be harnessed to improve poultry health and production efficiency. Notably, biotechnology-based approaches have fueled rapid advances in biological research, including (a) genetic manipulation in poultry breeding to improve the growth and egg production traits and disease resistance, (b) rapid identification of infectious agents using DNA-based approaches, (c) inclusion of natural and synthetic feed additives to poultry diets to enhance their nutritional value and maximize feed utilization by birds, and (d) production of biological products such as vaccines and various types of immunostimulants to increase the defensive activity of the immune system against pathogenic infection. Indeed, managing both existing and newly emerging infectious diseases presents a challenge for poultry production. However, recent strides in vaccine technology are demonstrating significant promise for disease prevention and control. This review focuses on the evolving applications of biotechnology aimed at enhancing vaccine immunogenicity, efficacy, stability, and delivery.

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Section: Vaccine Adjuvantsmentioning

confidence: 99%

Advances in Poultry Vaccines: Leveraging Biotechnology for Improving Vaccine Development, Stability, and Delivery

Abdelaziz,

Helmy,

Yitbarek

et al. 2024

Vaccines

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show abstract

“…Results of this trial are yet to be available. While having the advantage of avoiding the dangerous inflammatory “cytokine storm” ( 276 ), Entolimod has a drawback that it can induce a rapid antibody neutralization ( 277 ),leading to its efficacy limitation. Pharmacological modification could be one solution to this problem.…”

Section: Recent Advances Of Tlr-targeted Tumor Therapiesmentioning

confidence: 99%

“…Pharmacological modification could be one solution to this problem. Mett et al ( 277 ) identified and eliminated the epitopes leading to Entolimod’s neutralizing immunogenicity and refined its structure to get GP532 as a new TLR5 agonist. GP532 reduced neutralizing antibody response while preserving pro-inflammatory capacity.…”

Section: Recent Advances Of Tlr-targeted Tumor Therapiesmentioning

confidence: 99%

Toll-like receptor-targeted anti-tumor therapies: Advances and challenges

Yang

Fotopoulou

et al. 2022

Front. Immunol.

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Toll-like receptors (TLRs) are pattern recognition receptors, originally discovered to stimulate innate immune reactions against microbial infection. TLRs also play essential roles in bridging the innate and adaptive immune system, playing multiple roles in inflammation, autoimmune diseases, and cancer. Thanks to the immune stimulatory potential of TLRs, TLR-targeted strategies in cancer treatment have proved to be able to regulate the tumor microenvironment towards tumoricidal phenotypes. Quantities of pre-clinical studies and clinical trials using TLR-targeted strategies in treating cancer have been initiated, with some drugs already becoming part of standard care. Here we review the structure, ligand, signaling pathways, and expression of TLRs; we then provide an overview of the pre-clinical studies and an updated clinical trial watch targeting each TLR in cancer treatment; and finally, we discuss the challenges and prospects of TLR-targeted therapy.

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“…Another study states that TLR-5 agonist mediated by flagellin later activates the transcription factors like NFκB and AP-1. These cause expression of several antiapoptotic, ROS scavenging genes, can limit the radiation damage in normal cells (29). This can be a new avenue for chemotherapy adjuvants.…”

Section: Figmentioning

confidence: 99%

Microbiota milieu and mechanisms of intestinal Toll Like Receptors (TLRs) involved in chemotherapy induced mucositis

Marathe¹,

Rao²,

Rai³

2022

Biomedicine

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Gut is not only of digestive but also of immunological importance because of the residing microbiota milieu. Pathological or certain therapeutic condition may modify the normal commensal microflora. Mucositis, the most common untoward effect of chemotherapy, can also lead to this microbiotic imbalance. This shift leads to various molecular cascades which in turn trigger the action of Pattern Recognition Receptors (PRR’s). Toll like receptor (TLR) is one such pattern recognition receptor. In the human body there are about 13 types of TLRs out of which TLR-2, TLR-4, TLR-5 and TLR-9 are intestinal specific. They respond through ligands such as bacterial derivatives like flagellin, Lipoteichoic acid, Lipopolysaccharides, microbial antigen or genetic material of the viru. In turn via adaptor molecules, TLRs alter the signalling mechanisms and further induct the activation of pro or anti-inflammatory cytokines based on the immunological need. Several of the studies have described the involvement of under twined mechanisms of TLRs during chemotherapy. Therefore, agonists and/or antagonists of these strategic molecules may play a key role in pathological and therapeutic aspects. Thus, this review is an attempt to focus on the involvement of TLRs and microbiota to different chemotherapeutic agents and thereby track the available mechanisms of functionality.

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A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications

Cited by 17 publications

References 34 publications

Advances in Poultry Vaccines: Leveraging Biotechnology for Improving Vaccine Development, Stability, and Delivery

Advances in Poultry Vaccines: Leveraging Biotechnology for Improving Vaccine Development, Stability, and Delivery

Toll-like receptor-targeted anti-tumor therapies: Advances and challenges

Microbiota milieu and mechanisms of intestinal Toll Like Receptors (TLRs) involved in chemotherapy induced mucositis

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