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Advanced Science (Weinheim,... Nov 2023Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to...
Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to lymph nodes from intramuscular or subcutaneous injections. In difficult-to-transfect antigen-presenting cells (APCs), such as dendritic cells (DCs), effective mRNA transfection remains a significant challenge. In this study, a lymphatic targeting carrier using DC membranes is developed, that efficiently migrated to lymphoid organs, such as the spleen and lymph nodes. The nanoparticles contained an ionizable lipid (YK009), which ensured a high encapsulation efficacy of mRNA and assisted mRNA with endosomal escape after cellular uptake. Dendritic cell-mimicking nanoparticles (DCMNPs) showed efficient protein expression in both the spleen and lymph nodes after intramuscular injections. Moreover, in immunized mice, DCMNP vaccination elicited Spike-specific IgG antibodies, neutralizing antibodies, and Th1-biased SARS-CoV-2-specific cellular immunity. This work presents a powerful vaccine formula using DCMNPs, which represents a promising vaccine candidate for further research and development.
Topics: Mice; Animals; Dendritic Cells; RNA, Messenger; Nanoparticles; Immunity, Cellular; Vaccines
PubMed: 37867227
DOI: 10.1002/advs.202302423 -
Cancer Biotherapy & Radiopharmaceuticals Sep 2023Dendritic cells (DCs) are the most important antigen-presenting cells in the body and play a key role in antigen recognition, uptake, processing, and presentation and... (Review)
Review
Dendritic cells (DCs) are the most important antigen-presenting cells in the body and play a key role in antigen recognition, uptake, processing, and presentation and mediate nonspecific immunity and specific immunity. To summarize the main findings that DC vaccines are a new immunotherapy scheme combining the strengths of tumor antigens and DCs that can boost the body's identification and clearance of tumors. In this review, the authors focus on the biological characteristics of DCs, recent advances in the understanding of antitumor mechanisms, and the classification of DC vaccines. The current progress of DC-based vaccine immunotherapy for common tumors with high morbidity or mortality in China were systematically summarize. The DC vaccines combining the strengths of tumor antigens will provide directions to explore reasonable, safe, and effective combination immunotherapy strategies for tumors in the future.
Topics: Humans; China; Immunotherapy; Antigens, Neoplasm; Dendritic Cells
PubMed: 37699203
DOI: 10.1089/cbr.2023.0041 -
Critical Reviews in Immunology 2018Dendritic cells (DCs) and macrophages (MΦs) are antigen-presenting phagocytic cells found in many peripheral tissues of the human body, including the blood, lymph... (Review)
Review
Dendritic cells (DCs) and macrophages (MΦs) are antigen-presenting phagocytic cells found in many peripheral tissues of the human body, including the blood, lymph nodes, skin, and lung. They are vital to maintaining steady-state respiration in the human lung based on their ability to clear airways while also directing tolerogenic or inflammatory responses based on specific stimuli. Over the past three decades, studies have determined that there are multiple subsets of these two general cell types that exist in the airways and interstitium. Identifying these numerous subsets has proven challenging, especially with the unique microenvironments present in the lung. Cells found in the vasculature are not the same subsets found in the skin or the lung, as demonstrated by surface marker expression. By transcriptional profiling, these subsets show similarities but also major differences. Primary human lung cells and/ or tissues are difficult to acquire, particularly in a healthy condition. Additionally, surface marker screening and transcriptional profiling are continually identifying new DC and MΦ subsets. While the overall field is moving forward, we emphasize that more attention needs to focus on replicating the steady-state microenvironment of the lung to reveal the physiological functions of these subsets.
Topics: Animals; Dendritic Cells; Humans; Lung; Macrophages; Rest
PubMed: 30806245
DOI: 10.1615/CritRevImmunol.2018026459 -
Transplant International : Official... Aug 2017Although the occurrence of acute rejection was significantly reduced and the allograft survival at 1 year was massively improved by the development of pharmacological... (Review)
Review
Although the occurrence of acute rejection was significantly reduced and the allograft survival at 1 year was massively improved by the development of pharmacological immunosuppressive drugs, little progress has been made regarding long-term graft survival. Cell therapy appears to be an innovative and promising strategy to minimize the use of immunosuppression in transplantation and consequently increases long-term graft survival. The strength of cell therapy is that it will induce graft-specific tolerance and not a general immunosuppression of the patients. Several candidates, such as tolerogenic dendritic cells, have been gaining interest as an efficient means of promoting antigen-specific tolerance over recent years. Studies performed in rodent models have demonstrated the feasibility and efficacy of tolerogenic dendritic cells for the induction of tolerance in transplantation. In parallel, protocols to generate human tolerogenic dendritic cells in vitro have been defined, and some phase I clinical trials in autoimmune diseases have been recently performed to evaluate the safety of tolerogenic dendritic cell therapy. In this review, we will focus on the potential therapeutic interest of these cells in transplantation as well as their generation and characterization in humans. Finally, we will describe our current clinical trial using autologous tolerogenic dendritic cells in transplantation.
Topics: Animals; Cell Transplantation; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Dendritic Cells; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Immunotherapy; Kidney Transplantation; Models, Animal; Organ Transplantation; Transplantation Immunology; Transplantation Tolerance
PubMed: 27864897
DOI: 10.1111/tri.12889 -
Frontiers in Immunology 2022Gastrointestinal (GI) cancers occur in the alimentary tract and accessory organs. They exert a global burden with high morbidity and mortality. Inside the tumor... (Review)
Review
Gastrointestinal (GI) cancers occur in the alimentary tract and accessory organs. They exert a global burden with high morbidity and mortality. Inside the tumor microenvironment, dendritic cells (DCs) are the most efficient antigen-presenting cells and are necessary for adaptive immune responses such as T and B-cell maturation. However, the subsets of DCs revealed before were mostly based on flow cytometry and bulk sequencing. With the development of single-cell RNA sequencing (scRNA-seq), the tumor and microenvironment heterogeneity of GI cancer has been illustrated. In this review, we summarize the classification and development trajectory of dendritic cells at the single-cell level in GI cancer. Additionally, we focused on the interaction of DCs with T cells and their effect on the response to immunotherapy. Specifically, we focused on the newly identified tumor-infiltrating dendritic cells and discuss their potential function in antitumor immunity.
Topics: Gastrointestinal Neoplasms; Ascomycota; Immunotherapy; Dendritic Cells; Tumor Microenvironment
PubMed: 36505406
DOI: 10.3389/fimmu.2022.1007823 -
Molecular Carcinogenesis Feb 2022Presentation of tumor antigens is a critical step in producing a robust antitumor immune response. Classically tumor antigens are thought to be presented to both CD8 and... (Review)
Review
Presentation of tumor antigens is a critical step in producing a robust antitumor immune response. Classically tumor antigens are thought to be presented to both CD8 and CD4 T cells by professional antigen-presenting cells (pAPCs) like dendritic cells using major histocompatibility complexes (MHC) I and II. But recent evidence suggests that in the tumor microenvironment (TME) cells other than pAPCs are capable of presenting tumor antigens on both MHC I and II. The evidence currently available on tumor antigen presentation by epithelial cells, vascular endothelial cells (VECs), fibroblasts, and cancer cells is reviewed herein. We refer to these cell types in the TME as "amateur" APCs (aAPCs). These aAPCs greatly outnumber pAPCs in the TME and could, potentially, play a significant role in priming an antitumor immune response. This new evidence supports a different perspective on antigen presentation and suggests new approaches that can be taken in designing immunotherapies to increase T cell priming.
Topics: Antigen Presentation; Antigen-Presenting Cells; Antigens, Neoplasm; Dendritic Cells; Endothelial Cells; Humans; Tumor Microenvironment
PubMed: 34570920
DOI: 10.1002/mc.23354 -
Hematology/oncology Clinics of North... Jun 2020Tagraxofusp, a CD123-targeted immunotoxin, is the first FDA-approved treatment for patients 2 years and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN).... (Meta-Analysis)
Meta-Analysis Review
Tagraxofusp, a CD123-targeted immunotoxin, is the first FDA-approved treatment for patients 2 years and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN). It has been shown to be safe and effective in treatment-naïve and previously treated adult patients, with high rates of successful bridging to hematopoietic stem cell transplantation. The pediatric experience is more limited but demonstrates safety. Given the risk of potentially fatal capillary leak syndrome with tagraxofusp, judicious patient selection is recommended. Combination therapy with hypomethylating agents and/or BCL-2 inhibitors are rational next lines of investigation, especially in patients ineligible to receive high-dose chemotherapy.
Topics: Age Factors; Antineoplastic Agents; Clinical Trials as Topic; Combined Modality Therapy; Dendritic Cells; Disease Management; Humans; Myeloproliferative Disorders; Recombinant Fusion Proteins; Treatment Outcome
PubMed: 32336420
DOI: 10.1016/j.hoc.2020.01.005 -
Frontiers in Immunology 2019Cell reprogramming concepts have been classically developed in the fields of developmental and stem cell biology and are currently being explored for regenerative... (Review)
Review
Cell reprogramming concepts have been classically developed in the fields of developmental and stem cell biology and are currently being explored for regenerative medicine, given its potential to generate desired cell types for replacement therapy. Cell fate can be experimentally reversed or modified by enforced expression of lineage specific transcription factors leading to pluripotency or attainment of another somatic cell type identity. The possibility to reprogram fibroblasts into induced dendritic cells (DC) competent for antigen presentation creates a paradigm shift for understanding and modulating the immune system with direct cell reprogramming. PU.1, IRF8, and BATF3 were identified as sufficient and necessary to impose DC fate in unrelated cell types, taking advantage of Clec9a, a C-type lectin receptor with restricted expression in conventional DC type 1. The identification of such minimal gene regulatory networks helps to elucidate the molecular mechanisms governing development and lineage heterogeneity along the hematopoietic hierarchy. Furthermore, the generation of patient-tailored reprogrammed immune cells provides new and exciting tools for the expanding field of cancer immunotherapy. Here, we summarize cell reprogramming concepts and experimental approaches, review current knowledge at the intersection of cell reprogramming with hematopoiesis, and propose how cell fate engineering can be merged to immunology, opening new opportunities to understand the immune system in health and disease.
Topics: Animals; Cellular Reprogramming; Dendritic Cells; Hematopoiesis; Humans; Immunity; Immunotherapy
PubMed: 31921109
DOI: 10.3389/fimmu.2019.02809 -
Frontiers in Immunology 2023With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a... (Review)
Review
With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a successful strategy to develop innovative and potent vaccines. Indeed, it offers the potential to increase vaccine potency and/or modulate immune response quality while reducing off-target effects. With mRNA-vaccines establishing themselves as a versatile technology for future applications, in the last years several approaches have been explored to target nanoparticles-enabled mRNA-delivery systems to immune cells, with a focus on dendritic cells. Dendritic cells (DCs) are the most potent antigen presenting cells and key mediators of B- and T-cell immunity, and therefore considered as an ideal target for cell-specific antigen delivery. Indeed, improved potency of DC-targeted vaccines has been proved and . This review discusses the potential specific targets for immune system-directed mRNA delivery, as well as the different targeting ligand classes and delivery systems used for this purpose.
Topics: Dendritic Cells; Vaccines; Adaptive Immunity; T-Lymphocytes; Antigens
PubMed: 38090568
DOI: 10.3389/fimmu.2023.1294929 -
Immunobiology Feb 2015Cancer cells evolve from normal cells throughout life and are usually recognized by our immune system and destroyed, a process called immunosurveillance. Unfortunately,... (Review)
Review
Cancer cells evolve from normal cells throughout life and are usually recognized by our immune system and destroyed, a process called immunosurveillance. Unfortunately, in some instances cancer cells paralyze our immune system, resulting in outgrowth and spreading of the tumor. Understanding the complexity of immunomodulation by tumors is important for the development of therapeutical strategies. Nowadays, various approaches have been developed to enhance anti-tumor immune responses and abrogate the immune dampening effect of the tumor and its surrounding environment, including dendritic cell-based vaccines, therapies to counteract myeloid derived suppressor cell function within the tumor and antagonists of inhibitory signaling pathways to overcome 'immune checkpoints'. The challenge is now to find the right combination of immune based therapies to fully restore immune function and provide a more efficacious and enduring anti-tumor response.
Topics: Animals; Cancer Vaccines; Dendritic Cells; Humans; Immunomodulation; Immunotherapy; Monitoring, Immunologic; Neoplasms; Tumor Microenvironment
PubMed: 25466585
DOI: 10.1016/j.imbio.2014.11.007