Dendritic Nanomedicine with Boronate Bonds for Augmented Chemo‐Immunotherapy via Synergistic Modulation of Tumor Immune Microenvironment

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 25, 2023

Unsatisfied tumor accumulation of chemotherapeutic drugs and a complicated immunosuppressive microenvironment diminish the immune response rate therapeutic effect. Surface modification these with target ligands can promote their cellular internalization, but modified may be subjected to unexpected recognition clearance. Herein, phenylboronic acid (PBA) group-shieldable dendritic nanomedicine that integrates an immunogenic cell death (ICD)-inducing agent (epirubicin, Epi) indoleamine 2,3-dioxgenase 1 (IDO1) inhibitor (NLG919) is reported for chemo-immunotherapy. This NLG919-loaded Epi-conjugated PEGylated dendrimers bridged boronate bonds (NLG919@Epi-DBP) maintains stable nanostructure during circulation. Under moderate acidic condition, PBA group exposes sialic residue on membrane enhance internalization penetration NLG919@Epi-DBP. At pH 5.0, NLG919@Epi-DBP rapidly disassembles release incorporated Epi NLG919. triggers robust ICD cells evokes strong response. In addition, inhibition IDO1 activity downregulates metabolism L-tryptophan kynurenine, leading reduction in recruitment modulation microenvironment. Collectively, this promising strategy has been demonstrated evoke as well remodel enhanced chemo-immunotherapeutic

Language: Английский

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Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(6), P. e009063 - e009063

Published: June 1, 2024

Cancer immunotherapy has flourished over the last 10–15 years, transforming practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, bispecific T engagers, a vaccine, an oncolytic virus have joined cytokines as standard cancer care. At same scientific progress delivered vast amounts new knowledge. For example, advances in technologies such single-cell sequencing spatial transcriptomics provided deep insights into immunobiology tumor microenvironment. With rapid progress, field is currently at critical inflection point, with potential exponential growth next decade. Recognizing this, Society Immunotherapy convened diverse group experts representing academia, pharmaceutical biotechnology industries, patient advocacy, regulatory community identify current opportunities challenges goal prioritizing areas highest impact. The consensus identified seven high-priority opportunity field: mechanisms antitumor activity toxicity; drug resistance; biomarkers biospecimens; unique aspects novel therapeutics; host environmental interactions; premalignant immunity, interception, immunoprevention; trial design, endpoints, conduct. Additionally, roadblocks were discussed, several topics cross-cutting tools optimization, each impact multiple priority areas. These include preclinical models, data curation sharing, biopsies biospecimens, diversification funding sources, definitions standards, engagement. Finally, key guiding principles that will both optimize maximize field. engaging community; cultivating diversity, equity, inclusion, accessibility; leveraging power artificial intelligence accelerate progress. Here, we present outcomes these discussions strategic vision galvanize decade immunotherapy.

Language: Английский

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Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases

Immunity, Journal Year: 2024, Volume and Issue: 57(10), P. 2416 - 2432.e8

Published: Sept. 2, 2024

Language: Английский

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Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 6822 - 6838

Published: April 8, 2024

Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as carrier, in TLR1/2 agonist Pam3CSK4 was conjugated to N-terminus MUC1-loaded carrier BSA through pyridoxal 5′-phosphate-mediated transamination reaction. The resulting Pam3CSK4–BSA-MUC1 conjugate subsequently incorporated into liposomes, biomimics membrane structure tumor cells. results indicated that this significantly enhanced antigen uptake APCs and obviously augmented retention vaccine at injection site. Compared with BSA-MUC1 + groups, evoked 22- 11-fold increases MUC1-specific IgG titers. Importantly, elicited robust cellular immunity inhibited growth. This is first time constructed enhance immunogenicity, universal platform exhibits promise for utilization various vaccines, holding potential further clinical application.

Language: Английский

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Advancing Precision Medicine: Uncovering Biomarkers and Strategies to Mitigate Immune-Related Adverse Events in Immune Checkpoint Inhibitors Therapy

Toxicology Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102035 - 102035

Published: April 1, 2025

Language: Английский

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Immunological landscape of solid cancer: Interplay between tumor and autoimmunity

International review of cell and molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 163 - 235

Published: Jan. 1, 2024

Language: Английский

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Hyphae and Healthspan

Published: Aug. 1, 2024

Candida overgrowth (CO) can induce an avalanche of health problems. Its hyphal wall contains epitopes that trigger not only gluten type antibodies (celiac disease) but also a plethora mannan related targeting Gq coupled GPCRs. These latter disrupt autonomic receptors, inducing POTS, loss taste and smell, many other symptoms. auto-antibodies chemotactic cytokine receptors (CCRs) pain, psoriasis, alopecia areata, vitiligo maladies. They target T cells otherwise suppress latent viruses, e.g., EBV. Hyphae release candidalysin, toxin suppresses growth competing intestinal bacteria, triggers inflammasomes, causes hypercitrullination. Anti-citrullinated peptide (ACPAs) are produced. B exposed to hyper citrullination develop citrullinated receptors. ACPAs CCRs may jointly viral reactivation from infected cells. EBV, in virtually all humans now free circulate, is targeted by these same ACPAs. EBV nuclear material released antinuclear (ANAs) emerge. the histamine tryptase mast Tryptase have been tightly linked trifecta cell activation syndrome (MCAS), hypermobility spectrum disorder (HSD), POTS addition long Covid (LC) probably anti-phospholipid (APS). periodontitis. Bacteria generally considered be culprits, hyphae its biofilm facilitate their pathogenesis. Periodontitis with sentinel risk indicator for cancer, dementia, autoimmune disease, ASCVD chronic disease general. D3 tryptophan oppose invasive transition Candida, which responds releasing indoleamine dioxygenase degrades tryptophan. This altered metabolism characteristic these. Ultimately directly or indirectly involved gut dysbiosis, including periodontitis, detriment healthspan. The approach conceptual empirical.

Language: Английский

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Immune checkpoints in autoimmune vasculitis

Best Practice & Research Clinical Rheumatology, Journal Year: 2024, Volume and Issue: 38(2), P. 101943 - 101943

Published: May 1, 2024

Language: Английский

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Sex and Disease Regulate MHC I Expression in Human Lung Epithelial Cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 24, 2024

ABSTRACT Major histocompatibility complex class I (MHC I) molecules present endogenous peptides to CD8+ T-cells for immunosurveillance of infections and cancers. Recent studies revealed unexpected heterogeneity in MHC expression among cells different lineages. While respiratory diseases rank the leading causes mortality, mice showed that lung epithelial (LECs) express lower levels than all other tested cell types. The study aimed evaluate human LECs from parenchymal explants using single-cell RNA sequencing (scRNA-seq) immunostaining primary LECs. After confirming low constitutive LECs, we observed a significant upregulation across three chronic diseases: obstructive pulmonary disease (COPD), idiopathic fibrosis (IPF), cystic (CF). Additionally, unveiled an sexual dimorphism both health disease, with males exhibiting higher under steady-state conditions. Gene analyses suggest differential redox balance between sexes is instrumental this dimorphism. Our unveils interplay expression, sex, diseases. Since, models, contributes development immunopathologies, propose it might have similar impact on NEW & NOTEWORTHY This shows very healthy but escalates significantly diseases, potentially contributing progression. Furthermore, sex-specific divergences LEC hint at distinct susceptibilities inflammation females. Graphical abstract

Language: Английский

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The cryptic immunopeptidome in health and disease

Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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