Exploration of Pattern Recognition Receptor Agonists as Candidate Adjuvants

Frontiers in Cellular and Infection Microbiology, Journal Year: 2021, Volume and Issue: 11

Published: Oct. 6, 2021

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

Language: Английский

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Local scaffold-assisted delivery of immunotherapeutic agents for improved cancer immunotherapy

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 185, P. 114308 - 114308

Published: April 23, 2022

Language: Английский

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Multifunctional Lipid Bilayer Nanocarriers for Cancer Immunotherapy in Heterogeneous Tumor Microenvironments, Combining Immunogenic Cell Death Stimuli with Immune Modulatory Drugs

ACS Nano, Journal Year: 2022, Volume and Issue: 16(4), P. 5184 - 5232

Published: March 29, 2022

In addition to the contribution of cancer cells, solid tumor microenvironment (TME) has a critical role in determining expansion, antitumor immunity, and response immunotherapy. Understanding details complex interplay between cells components TME provides an unprecedented opportunity explore combination therapy for intervening immune landscape improve immunotherapy outcome. One approach is introduction multifunctional nanocarriers, capable delivering drug combinations that provide immunogenic stimuli improvement antigen presentation, contemporaneous with delivery coformulated or synthetic molecules danger signals interfere immune-escape, immune-suppressive, T-cell exclusion pathways. This forward-looking review will discuss use lipid-bilayer-encapsulated liposomes mesoporous silica nanoparticles heterogeneous landscapes pancreatic ductal adenocarcinoma triple-negative breast cancer. We describe how remote loading lipid bilayer encapsulation used synthesis synergistic induce cell death, PD-1/PD-L1 axis, inhibit indoleamine-pyrrole 2,3-dioxygenase (IDO-1) metabolic pathway, restore spatial access activated T-cells site, reduce impact immunosuppressive stromal components. show integration current knowledge future discovery can be rational nanoenabled

Language: Английский

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Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice

npj Vaccines, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 23, 2022

Adjuvants enhance the magnitude and durability of immune response to vaccines. However, there is a paucity comparative studies on nature responses stimulated by leading adjuvant candidates. In this study, we compared five clinically relevant adjuvants in mice-alum, AS03 (a squalene-based supplemented with α-tocopherol), AS37 TLR7 ligand emulsified alum), CpG1018 TLR9 O/W 1849101 adjuvant)-for their capacity stimulate when combined subunit vaccine under clinical development. We found that all four candidates surpassed alum respect induce enhanced durable antigen-specific antibody responses. The TLR-agonist-based (TLR9) (TLR7) induced Th1-skewed CD4+ T cell responses, while alum, O/W, balanced Th1/Th2 response. Consistent this, distinct patterns early innate Finally, vaccines adjuvanted AS03, AS37, CpG1018/alum-induced neutralizing-antibody significant protection against B.1.351 variant 7 months following immunization. These results, together our recent results from an identical study non-human primates (NHPs), provide benchmarking for immunity vaccine, demonstrating SARS-CoV-2 variant. Furthermore, these reveal differences between widely-used C57BL/6 mouse strain NHP animal models, highlighting importance species selection future studies.

Language: Английский

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Nanocarrier Co-formulation for Delivery of a TLR7 Agonist plus an Immunogenic Cell Death Stimulus Triggers Effective Pancreatic Cancer Chemo-immunotherapy

ACS Nano, Journal Year: 2022, Volume and Issue: 16(8), P. 13168 - 13182

Published: Aug. 3, 2022

Although toll-like receptor (TLR) agonists hold great promise as immune modulators for reprogramming the suppressive landscape in pancreatic ductal adenocarcinoma (PDAC), their use is limited by poor pharmacokinetics (PK) and off-target systemic inflammatory effects. To overcome these challenges well to attain drug synergy, we developed a lipid bilayer (LB)-coated mesoporous silica nanoparticle (silicasome) platform co-delivery of TLR7/8 agonist 3M-052 with immunogenic chemotherapeutic agent irinotecan. This was accomplished incorporating C18 tail coated LB, also useful irinotecan remote loading porous interior. Not only did co-formulated carrier improve PK, but it strengthened irinotecan-induced cell death response 3M-052-mediated dendritic activation at tumor site participating lymph nodes. The accompanying increase CD8

Language: Английский

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Photoactivatable nanoagonists chemically programmed for pharmacokinetic tuning and in situ cancer vaccination

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(8)

Published: Feb. 14, 2023

Immunotherapy holds great promise for the treatment of aggressive and metastatic cancers; however, currently available immunotherapeutics, such as immune checkpoint blockade, benefit only a small subset patients. A photoactivatable toll-like receptor 7/8 (TLR7/8) nanoagonist (PNA) system that imparts near-infrared (NIR) light-induced immunogenic cell death (ICD) in dying tumor cells synchrony with spontaneous release potent immunoadjuvant is developed here. The PNA consists polymer-derived proimmunoadjuvants ligated via reactive oxygen species (ROS)-cleavable linker photosensitizers, which are further encapsulated amphiphilic matrices systemic injection. In particular, conjugation TLR7/8 agonist resiquimod to biodegradable macromolecular moieties different molecular weights enabled pharmacokinetic tuning small-molecule agonists optimized delivery efficiency mice. Upon NIR photoirradiation, effectively generated ROS not ablate tumors induce ICD cascade but also trigger on-demand TLR agonists. several preclinical cancer models, intravenous administration followed by irradiation resulted remarkable regression suppressed postsurgical recurrence metastasis. Furthermore, this profoundly shifted landscape tumoricidal one, eliciting robust tumor-specific T priming vivo. This work highlights simple cost-effective approach generate situ vaccines synergistic photodynamic immunotherapy cancers.

Language: Английский

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Engineering kinetics of TLR7/8 agonist release from bottlebrush prodrugs enables tumor-focused immune stimulation

Science Advances, Journal Year: 2023, Volume and Issue: 9(16)

Published: April 19, 2023

Imidazoquinolines (IMDs), such as resiquimod (R848), are of great interest potential cancer immunotherapies because their ability to activate Toll-like receptor 7 (TLR7) and/or TLR8 on innate immune cells. Nevertheless, intravenous administration IMDs causes severe immune-related toxicities, and attempts improve tissue-selective exposure while minimizing acute systemic inflammation have proven difficult. Here, using a library R848 "bottlebrush prodrugs" (BPDs) that differ only by release kinetics, we explore how the timing affects stimulation in vitro vivo. These studies led discovery R848-BPDs exhibit optimal activation kinetics achieve potent myeloid cells tumors substantial reductions tumor growth following mouse syngeneic models without any observable toxicity. results suggest can be tuned at molecular level provide safe yet effective systemically administered immunostimulant prodrugs for next-generation immunotherapies.

Language: Английский

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Advancements in Vaccine Adjuvants: The Journey from Alum to Nano Formulations

Vaccines, Journal Year: 2023, Volume and Issue: 11(11), P. 1704 - 1704

Published: Nov. 9, 2023

Vaccination is a groundbreaking approach in preventing and controlling infectious diseases. However, the effectiveness of vaccines can be greatly enhanced by inclusion adjuvants, which are substances that potentiate modulate immune response. This review based on extensive searches reputable databases such as Web Science, PubMed, EMBASE, Scopus, Google Scholar. The goal this to provide thorough analysis advances field adjuvant research, trace evolution, understand effects various adjuvants. Historically, alum was pioneer adjuvants because it first approved for use humans. It served foundation subsequent research innovation field. As science progressed, shifted identifying exploiting potential newer One important area interest nano formulations. These advanced have special properties tailored enhance response vaccines. transition from traditional alum-based formulations indicative dynamism vaccine research. Innovations particularly development formulations, promising step toward improving efficacy safety. redefine boundaries vaccination potentially expand range diseases addressed with approach. There an optimistic view future improved will contribute significantly global health outcomes.

Language: Английский

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Supramolecular Biomaterials for Cancer Immunotherapy

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with feeble immune responses serious adverse effects still cannot be neglected due to the complicated multifactorial etiology pathologic microenvironment tumors. The rapid development of nanomedical science material facilitated advanced progress engineering biomaterials tackle critical issues. supramolecular flexible modular structures have exhibited unparalleled advantages high cargo-loading efficiency, excellent biocompatibility, diversiform immunomodulatory activity, thereby providing a powerful weapon for cancer immunotherapy. In past decades, were extensively explored as versatile delivery platforms immunotherapeutic agents or designed interact key moleculars system precise controllable manner. this review, we focused on crucial role modulation pivotal steps during immunotherapy, including antigen presentation, T lymphocyte activation, tumor-associated macrophage elimination repolarization, myeloid-derived suppressor cell depletion. Based extensive research, current prospects

Language: Английский

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Nanoparticle-based immunoengineering strategies for enhancing cancer immunotherapy

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 365, P. 773 - 800

Published: Dec. 14, 2023

Language: Английский

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