Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 165 - 165

Published: Feb. 6, 2024

Dendritic cells (DCs) serve as professional antigen-presenting (APC) bridging innate and adaptive immunity, playing an essential role in triggering specific cellular humoral responses against tumor infectious antigens. Consequently, various DC-based antitumor therapeutic strategies have been developed, particularly vaccines, intensively investigated specifically the context of acute myeloid leukemia (AML). This hematological malignancy mainly affects elderly population (those aged over 65), which usually presents a high rate failure unfavorable prognosis. In this review, we examine current state development progress vaccines AML. The findings evidence possible administration adjuvant treatment AML following initial therapy. Furthermore, therapy demonstrates promising outcomes preventing or delaying relapse exhibits synergistic effects when combined with other treatments during relapses disease progression. On hand, remarkable success observed RNA for COVID-19, delivered lipid nanoparticles, has revealed efficacy effectiveness these types vectors, prompting further exploration their potential application AML, well neoplasms, loading them RNA.

Language: Английский

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Advances in targeted delivery of mRNA into immune cells for enhanced cancer therapy

Theranostics, Journal Year: 2024, Volume and Issue: 14(14), P. 5528 - 5550

Published: Jan. 1, 2024

Messenger RNA (mRNA) therapy has been applied to the treatment of various human diseases including malignant tumors. Increasing evidences have shown that mRNA can enhance efficacy cancer immunotherapy by modulating functions immune cells and stimulating their activity. However, is a type negatively charged biomacromolecules are susceptible serum nucleases cannot readily cross cell membrane. In past few decades, nanoparticles (NPs)-based delivery systems rationally designed developed facilitate intracellular uptake cytosolic mRNA. More importantly, means specific recognition between targeting ligands decorated on NP surface receptors specifically expressed cells, these could be functionalized target further mRNA-based immunotherapy. this review, we briefly introduced advancements in therapy, discussed challenges faced delivery, systematically summarized recent development NPs-based types for The future NPs-mediated targeted clinical translation also discussed.

Language: Английский

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Muco‐Penetrating Lipid Nanoparticles Having a Liquid Core for Enhanced Intranasal mRNA Delivery

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract Intranasal delivery of mRNA vaccines offers promising opportunities to combat airborne viruses like SARS‐CoV‐2 by provoking mucosal immunity, which not only defends against respiratory infection but also prevents contagious transmission. However, the development nasal has been hampered lack effective means overcome mucus barrier. Herein, ionizable lipid‐incorporated liquid lipid nanoparticles (iLLNs) capable delivering cargo across airway mucosa are designed. Adjusting ratios and cationic lipids allows fine‐tuning p K a iLLNs range pH (5.5–6.5), thus facilitating penetration via formation near‐neutral, PEGylated muco‐inert surfaces. When nasally administered mice, top candidate iLLN‐2/mRNA complexes enable about 60‐fold greater reporter gene expression in cavity, compared benchmark mRNA‐lipid (ALC‐LNP) having same composition as that BNT162b2 vaccine. Moreover, prime‐boost intranasal immunization elicits magnitude spike‐specific IgA IgG response than ALC‐LNP, without triggering any noticeable inflammatory reactions. Taken together, these results provide useful insights for design deliverable formulations prophylactic applications.

Language: Английский

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An mRNA vaccine encoding proteasome-targeted antigen enhances CD8+ T cell immunity

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 381, P. 113578 - 113578

Published: Feb. 26, 2025

Language: Английский

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Machine learning-assisted design of immunomodulatory lipid nanoparticles for delivery of mRNA to repolarize hyperactivated microglia

Drug Delivery, Journal Year: 2025, Volume and Issue: 32(1)

Published: March 3, 2025

Regulating inflammatory microglia presents a promising strategy for treating neurodegenerative and autoimmune disorders, yet effective therapeutic agents delivery to these cells remains challenge. This study investigates modified lipid nanoparticles (LNP) mRNA hyperactivated microglia, particularly those with pro-inflammatory characteristics, utilizing supervised machine learning (ML) classifiers. We developed screened library of 216 LNP formulations varying compositions, N/P ratios, hyaluronic acid (HA) modifications. The transfection efficiency eGFP was assessed in the BV-2 murine cell line under different immunological states, including resting activated conditions (LPS-activated IL4/IL13-activated). ML-guided morphometric analysis tracked phenotypes various subtypes before after transfection. Four ML classifiers were investigated predict phenotypic changes based on design parameters. Multi-Layer Perceptron (MLP) neural network emerged as best-performing model, achieving weighted F1-scores ≥0.8. While it accurately predicted responses from LPS-activated cells, struggled IL4/IL13-activated cells. MLP model validated by predicting performance four unseen delivering BV2 HA-LNP2 optimal formulation target IL10 mRNA, effectively suppressing phenotypes, evidenced shifts morphology, increased expression, reduced TNF-α levels. also evaluated human iPSC-derived confirming its efficacy modulating responses. highlights potential tailored techniques enhance therapy neuroinflammatory disorders leveraging carrier's immunogenic properties modulate microglial

Language: Английский

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