Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants

Bhagchandani, Sachin; Johnson, Jeremiah A.; Irvine, Darrell J.

doi:10.1016/j.addr.2021.05.013

Cited by 83 publications

(94 citation statements)

References 360 publications

(300 reference statements)

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“…Thus, many clinical trials combining TLR3 agonists and ICBs are in progress (Table 1 ). So far, about 18 TLR7/8 agonists are used in clinical trials for the treatment of cancer and infections [ 119 ]. Some of them are combined with ICBs to treat cancers in phase 1/2 (Table 1 ).…”

Section: Tlr Agonistsmentioning

confidence: 99%

Type I interferon-mediated tumor immunity and its role in immunotherapy

Zhu

Chen

2022

Cell. Mol. Life Sci.

107

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Immune checkpoint blockade (ICB) therapies have achieved remarkable clinical responses in patients with many different types of cancer; however, most patients who receive ICB monotherapy fail to achieve long-term responses, and some tumors become immunotherapy-resistant and even hyperprogressive. Type I interferons (IFNs) have been demonstrated to inhibit tumor growth directly and indirectly by acting upon tumor and immune cells, respectively. Furthermore, accumulating evidence indicates that endo- and exogenously enhancing type I IFNs have a synergistic effect on anti-tumor immunity. Therefore, clinical trials studying new treatment strategies that combine type I IFN inducers with ICB are currently in progress. Here, we review the cellular sources of type I IFNs and their roles in the immune regulation of the tumor microenvironment. In addition, we highlight immunotherapies based on type I IFNs and combination therapy between type I IFN inducers and ICBs.

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Section: Tlr Agonistsmentioning

confidence: 99%

Type I interferon-mediated tumor immunity and its role in immunotherapy

Zhu

Chen

2022

Cell. Mol. Life Sci.

107

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“…Some previous studies carried out the direct conjugation of imidazoquinolines to HIV-1 Gag protein or whole inactivated influenza viruses, increasing Th1 responses and the number of antigen-specific T cells [ 196 , 197 , 198 ]. Moreover, conjugation to synthetic polymer scaffolds, lipid-polymer amphiphiles, polyethylene glycol (PEG), nanogels, alum, and various other synthetic polymers remarkably increased the delivery of imidazoquinolines and improved the maturation of DCs and antigen-specific T cells [ 199 ]. Moreover, previous studies using a mix of imidazoquinolines with one or more other TLR agonists, such as MPLA (TLR4) and MPLA + CpG ODN (TLR4 and TLR9), showed that this combination increased innate immune responses, with remarkable production of antigen-specific neutralising antibodies and improved Th1 responses [ 200 , 201 , 202 ].…”

Section: Immune Potentiatorsmentioning

confidence: 99%

An Overview of Vaccine Adjuvants: Current Evidence and Future Perspectives

et al. 2022

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Vaccinations are one of the most important preventive tools against infectious diseases. Over time, many different types of vaccines have been developed concerning the antigen component. Adjuvants are essential elements that increase the efficacy of vaccination practises through many different actions, especially acting as carriers, depots, and stimulators of immune responses. For many years, few adjuvants have been included in vaccines, with aluminium salts being the most commonly used adjuvant. However, recent research has focused its attention on many different new compounds with effective adjuvant properties and improved safety. Modern technologies such as nanotechnologies and molecular biology have forcefully entered the production processes of both antigen and adjuvant components, thereby improving vaccine efficacy. Microparticles, emulsions, and immune stimulators are currently in the spotlight for their huge potential in vaccine production. Although studies have reported some potential side effects of vaccine adjuvants such as the recently recognised ASIA syndrome, the huge worth of vaccines remains unquestionable. Indeed, the recent COVID-19 pandemic has highlighted the importance of vaccines, especially in regard to managing future potential pandemics. In this field, research into adjuvants could play a leading role in the production of increasingly effective vaccines.

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“…Some other conjugate formulations include intentional design of conjugate formulations that forms large particulates. Conjugation to synthetic polymer scaffolds, nanogels, lipidpolymer amphiphiles, alum, polyethylene glycol (PEG), or various other synthetic polymers has significantly improved delivery of TLR7/8 agonists, and increased mature DCs and antigen-specific T cells [extensively reviewed in (Bhagchandani et al, 2021)]. Another interesting attempt to deliver TLR7 agonists is using an oxidation-sensitive polymersome based on PEG-b-PPS reported by Scott et al (2012).…”

Section: Tlr7/8 Agonistsmentioning

confidence: 99%

Exploration of Pattern Recognition Receptor Agonists as Candidate Adjuvants

Ong

Lian

Kawasaki

et al. 2021

Front. Cell. Infect. Microbiol.

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Adjuvants are used to maximize the potency of vaccines by enhancing immune reactions. Components of adjuvants include pathogen-associated molecular patterns (PAMPs) and damage-associate molecular patterns (DAMPs) that are agonists for innate immune receptors. Innate immune responses are usually activated when pathogen recognition receptors (PRRs) recognize PAMPs derived from invading pathogens or DAMPs released by host cells upon tissue damage. Activation of innate immunity by PRR agonists in adjuvants activates acquired immune responses, which is crucial to enhance immune reactions against the targeted pathogen. For example, agonists for Toll-like receptors have yielded promising results as adjuvants, which target PRR as adjuvant candidates. However, a comprehensive understanding of the type of immunological reaction against agonists for PRRs is essential to ensure the safety and reliability of vaccine adjuvants. This review provides an overview of the current progress in development of PRR agonists as vaccine adjuvants, the molecular mechanisms that underlie activation of immune responses, and the enhancement of vaccine efficacy by these potential adjuvant candidates.

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Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants

Cited by 83 publications

References 360 publications

Type I interferon-mediated tumor immunity and its role in immunotherapy

Type I interferon-mediated tumor immunity and its role in immunotherapy

An Overview of Vaccine Adjuvants: Current Evidence and Future Perspectives

Exploration of Pattern Recognition Receptor Agonists as Candidate Adjuvants

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