Vaccine adjuvants: mechanisms and platforms

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 19, 2023

Abstract Adjuvants are indispensable components of vaccines. Despite being widely used in vaccines, their action mechanisms not yet clear. With a greater understanding the by which innate immune response controls antigen-specific response, adjuvants’ beginning to be elucidated. can categorized as immunostimulants and delivery systems. Immunostimulants danger signal molecules that lead maturation activation antigen-presenting cells (APCs) targeting Toll-like receptors (TLRs) other pattern recognition (PRRs) promote production antigen signals co-stimulatory signals, turn enhance adaptive responses. On hand, systems carrier materials facilitate presentation prolonging bioavailability loaded antigens, well antigens lymph nodes or APCs. The systematically summarized at this review. This is followed an introduction mechanisms, properties, progress classical vaccine adjuvants. Furthermore, since some adjuvants under investigation exhibit potency than adjuvants, could compensate for deficiencies summary adjuvant platforms subsequently presented. Notably, we highlight different immunological properties these platforms, will provide wide range options rational design basis, review points out development prospects problems should paid attention future.

Язык: Английский

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Engineering Radiosensitizer‐Based Metal‐Phenolic Networks Potentiate STING Pathway Activation for Advanced Radiotherapy

Advanced Materials, Год журнала: 2021, Номер 34(10)

Опубликована: Дек. 29, 2021

Radiotherapy, a mainstay of first-line cancer treatment, suffers from its high-dose radiation-induced systemic toxicity and radioresistance caused by the immunosuppressive tumor microenvironment. The synergy between radiosensitization immunomodulation may overcome these obstacles for advanced radiotherapy. Here, authors propose cooperated with stimulator interferon genes (STING) pathway activation strategy fabricating novel lanthanide-doped radiosensitizer-based metal-phenolic network, NaGdF4 :Nd@NaLuF4 @PEG-polyphenol/Mn (DSPM). amphiphilic PEG-polyphenol successfully coordinates (radiosensitizer) Mn2+ via robust coordination. After cell internalization, pH-responsive disassembly DSPM triggers release their payloads, wherein radiosensitizer sensitizes cells to X-ray promote STING activation. This remarkably benefits dendritic maturation, anticancer therapeutics in primary tumors, accompanied immune therapeutic performance against metastatic tumors. Therefore, powerful mediated immunostimulation is highlighted here optimize

Язык: Английский

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Chemically programmed STING-activating nano-liposomal vesicles improve anticancer immunity

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июль 31, 2023

Abstract The often immune-suppressive tumor microenvironment (TME) may hinder immune evasion and response to checkpoint blockade therapies. Pharmacological activation of the STING pathway does create an immunologically hot TME, however, systemic delivery might lead undesired off-target inflammatory responses. Here, we generate a small panel esterase-activatable pro-drugs based on structure non-nucleotide agonist MSA-2 that are subsequently stably incorporated into liposomal vesicle for intravenous administration. pharmacokinetic properties stimulatory capacity delivered via liposomes (SAProsomes) enhanced compared free drug form. By performing efficacy screening among SAProsomes incorporating different in syngeneic mouse models, find superior therapeutic performance relies improved desired lymphoid compartments. best candidate, SAProsome-3, highly stimulates secretion cytokines creates tumoricidal landscape. Notably, upon application breast cancer or melanoma SAProsome-3 elicits durable remission established tumors postsurgical tumor-free survival while decreasing metastatic burden without significant toxicity. In summary, our work establishes proof principle better targeted more efficient safe therapy.

Язык: Английский

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Materials engineering strategies for cancer vaccine adjuvant development

Chemical Society Reviews, Год журнала: 2023, Номер 52(9), С. 2886 - 2910

Опубликована: Янв. 1, 2023

Cancer vaccines have emerged as a powerful new tool for cancer immunotherapy. Adjuvants are vaccine ingredients that enhance the strength, velocity, and duration of immune response. The success adjuvants in achieving stable, safe, immunogenic has generated enthusiasm adjuvant development. Specifically, advances materials science providing insights into rational design topical Here, we outline current state engineering strategies, including those based on molecular adjuvants, polymers/lipids, inorganic nanoparticles, bio-derived materials, We also elaborate how these strategies physicochemical features involved influence effects adjuvants.

Язык: Английский

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Mitochondrial DNA-triggered innate immune response: mechanisms and diseases

Cellular and Molecular Immunology, Год журнала: 2023, Номер 20(12), С. 1403 - 1412

Опубликована: Ноя. 7, 2023

Abstract Various cellular stress conditions trigger mitochondrial DNA (mtDNA) release from mitochondria into the cytosol. The released mtDNA is sensed by cGAS-MITA/STING pathway, resulting in induced expression of type I interferon and other effector genes. These processes contribute to innate immune response viral infection factors. deregulation these causes autoimmune diseases, inflammatory metabolic disorders cancer. Therefore, pathway a potential target for intervention infectious, diseases as well In this review, we focus on mechanisms underlying mtDNA-triggered activation effects under various physiological pathological conditions, advances development drugs that cGAS MITA/STING.

Язык: Английский

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From structural design to delivery: mRNA therapeutics for cancer immunotherapy

Exploration, Год журнала: 2023, Номер 4(2)

Опубликована: Ноя. 17, 2023

Abstract mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority expressing all sequence‐known proteins vivo. In particular, a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens present epitopes to T lymphocytes elicit antitumor effects. addition, receptors like chimeric antigen receptor (CAR), T‐cell (TCR), CD134, immune‐modulating factors including cytokines, interferons, antibodies specific enhance immunological response against tumors. With the maturation vitro transcription (IVT) technology, large‐scale pure encoding be synthesized quickly. However, clinical translation mRNA‐based anticancer strategies is restricted by delivering into target organs or inadequate endosomal escape efficiency mRNA. Recently, there been some advances immunotherapy, which roughly classified modifications structure development delivery systems, especially lipid nanoparticle platforms. this review, latest overcoming limitations immunotherapies recent are summarized. Challenges opportunities applications also discussed.

Язык: Английский

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Sono‐Driven STING Activation using Semiconducting Polymeric Nanoagonists for Precision Sono‐Immunotherapy of Head and Neck Squamous Cell Carcinoma

Advanced Materials, Год журнала: 2023, Номер 35(30)

Опубликована: Апрель 29, 2023

Immunotherapy has offered new opportunities to treat head and neck squamous cell carcinoma (HNSCC); however, its clinical applications are hindered by modest therapeutic outcomes the "always-on" pharmacological activity of immunomodulatory agents. Strategies for precise spatiotemporal activation antitumor immunity can tackle these issues but remain challenging. Herein, a semiconducting polymeric nanoagonist (SPNM) with in situ sono-activatable immunotherapeutic effects precision sono-immunotherapy HNSCC is reported. SPNM self-assembled from sonodynamic polymer core conjugated stimulator interferon genes (STING) agonist (MSA-2) via singlet oxygen cleavable linker. Under sono-irradiation, produces not only eradicate tumor cells trigger immunogenic death also unleash caged STING agonists cleavage diphenoxyethene bonds pathway region. Such sono-driven mediated promotes effector T infiltration potentiates systemic immunity, eventually leading growth inhibition long-term immunological memory. This study thus presents promising strategy cancer immunotherapy.

Язык: Английский

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From periphery to center stage: 50 years of advancements in innate immunity

Cell, Год журнала: 2024, Номер 187(9), С. 2030 - 2051

Опубликована: Апрель 1, 2024

Over the past 50 years in field of immunology, something a Copernican revolution has happened. For long time, immunologists were mainly concerned with what is termed adaptive immunity, which involves exquisitely specific activities lymphocytes. But other arm so-called "innate immunity," had been neglected. To celebrate Cell's 50th anniversary, we have put together review processes and components innate immunity trace seminal contributions leading to modern state this field. Innate joined center interest for all those who study body's defenses, as well homeostasis pathology. We are now entering era where therapeutic targeting immune receptors downstream signals hold substantial promise infectious inflammatory diseases cancer.

Язык: Английский

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A Cancer Nanovaccine for Co-Delivery of Peptide Neoantigens and Optimized Combinations of STING and TLR4 Agonists

ACS Nano, Год журнала: 2024, Номер 18(9), С. 6845 - 6862

Опубликована: Фев. 22, 2024

Immune checkpoint blockade (ICB) has revolutionized cancer treatment and led to complete durable responses, but only for a minority of patients. Resistance ICB can largely be attributed insufficient number and/or function antitumor CD8+ T cells in the tumor microenvironment. Neoantigen targeted vaccines activate expand cell repertoire, historically, clinical responses have been poor because immunity against peptide antigens is typically weak, resulting activation cytotoxic cells. Herein, we describe nanoparticle vaccine platform that overcome these barriers several ways. First, reproducibly formulated using scalable confined impingement jet mixing method coload variety physicochemically diverse multiple adjuvants into pH-responsive, vesicular nanoparticles are monodisperse less than 100 nm diameter. Using this approach, encapsulated synergistically acting adjuvants, cGAMP monophosphoryl lipid A (MPLA), nanocarrier induce robust tailored innate immune response increased antigen immunogenicity. We found incorporating both nanovaccine enhanced expression dendritic costimulatory markers, pro-inflammatory cytokine secretion, cross-presentation. Additionally, delivery lymph node accumulation uptake by draining node. Consequently, codelivery antigen, cGAMP, MPLA antigen-specific delayed growth mouse models. Finally, improved efficacy immunotherapy murine colon carcinoma model. This work establishes versatile neoantigens synergistic enhance vaccines.

Язык: Английский

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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(5), С. 2194 - 2209

Опубликована: Март 2, 2024

Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered application. To address this issue, we constructed a cell membrane-coated nanosystem (mB4S) reverse immuno-supportive one strengthening anti-tumor effect. In system, Epirubicin (EPI) as immunogenic death (ICD) inducer was coupled branched glycopolymer

Язык: Английский

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