Ex Vivo-Generated Tolerogenic Dendritic Cells: Hope for a Definitive Therapy of Autoimmune Diseases.

Current therapies for autoimmune diseases are immunosuppressant agents, which have many debilitating side effects. However, dendritic cells (DCs) can induce antigen-specific tolerance. Tolerance restoration mediated by ex vivo-generated DCs can be a therapeutic approach. Therefore, in this review, we summarize the conceptual framework for developing ex vivo-generated DC strategies for autoimmune diseases. First, we will discuss the role of DCs in developing immune tolerance as a foundation for developing dendritic cell-based immunotherapy for autoimmune diseases. Then, we also discuss relevant findings from pre-clinical and clinical studies of ex vivo-generated DCs for therapy of autoimmune diseases. Finally, we discuss problems and challenges in dendritic cell therapy in autoimmune diseases. Throughout the article, we discuss autoimmune diseases, emphasizing SLE.

Significant improvement of systemic lupus erythematosus manifestation in children after autologous dendritic cell transfer: a case report and review of literature.

Dendritic cells (DC) are postulated to play a role in autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We reported a 13-year-old female SLE patient who presents with chronic arthritis accompanied by persistent fever, dyspnea, sleep disturbance, headache, stomatitis, rash, and muscle weakness. The supporting examinations showed abnormal blood cell counts, positive antinuclear antibody profile, serositis, and neuropathy. Immunosuppressants failed to improve the condition. DC-based vaccine derived from autologous peripheral blood which was introduced with SARS-CoV-2 protein was given to this patient. There was a significant improvement in clinical and laboratory findings. Thus, DC immunotherapy appears to be a potential novel therapy for SLE that needs to be studied.

Safety and efficacy of dendritic cell vaccine for COVID-19 prevention after 1-Year follow-up: phase I and II clinical trial final result.

Introduction: Interim analysis of phase I and phase II clinical trials of personalized vaccines made from autologous monocyte-derived dendritic cells (DCs) incubated with S-protein of SARS-CoV-2 show that this vaccine is safe and well tolerated. Our previous report also indicates that this vaccine can induce specific T-cell and B cell responses against SARS-CoV-2. Herein, we report the final analysis after 1 year of follow-up regarding its safety and efficacy in subjects of phase I and phase II clinical trials. Methods: Adult subjects (>18 years old) were given autologous DCs derived from peripheral blood monocytes, which were incubated with the S-protein of SARS-CoV-2. The primary outcome is safety in phase I clinical trials. Meanwhile, optimal antigen dosage is determined in phase II clinical trials. Corona Virus Disease 2019 (COVID-19) and Non-COVID-19 adverse events (AEs) were observed for 1 year. Results: A total of 28 subjects in the phase I clinical trial were randomly assigned to nine groups based on antigen and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) dosage. In the phase II clinical trial, 145 subjects were randomly grouped into three groups based on antigen dosage. During the 1-year follow-up period, 35.71% of subjects in phase I and 16.54% in phase II had non-COVID AEs. No subjects in phase I experienced moderate-severe COVID-19. Meanwhile, 4.31% of subjects in phase II had moderate-severe COVID-19. There is no difference in both COVID and non-COVID-19 AEs between groups. Conclusions: After 1 year of follow-up, this vaccine is proven safe and effective for preventing COVID-19. A phase III clinical trial involving more subjects should be conducted to establish its efficacy and see other possible side effects.

Developing dendritic cell for SARS-CoV-2 vaccine: Breakthrough in the pandemic.

Finding a vaccine that can last a long time and effective against viruses with high mutation rates such as SARS-CoV-2 is still a challenge today. The various vaccines that have been available have decreased in effectiveness and require booster administration. As the professional antigen presenting cell, Dendritic Cells can also activate the immune system, especially T cells. This ability makes dendritic cells have been developed as vaccines for some types of diseases. In SARS-CoV-2 infection, T cells play a vital role in eliminating the virus, and their presence can be detected in the long term. Hence, this condition shows that the formation of T cell immunity is essential to prevent and control the course of the disease. The construction of vaccines oriented to induce strong T cells response can be formed by utilizing dendritic cells. In this article, we discuss and illustrate the role of dendritic cells and T cells in the pathogenesis of SARS-CoV-2 infection and summarizing the crucial role of dendritic cells in the formation of T cell immunity. We arrange the basis concept of developing dendritic cells for SARS-CoV-2 vaccines. A dendritic cell-based vaccine for SARS-CoV-2 has the potential to be an effective vaccine that solves existing problems.

Dendritic cell vaccine as a potential strategy to end the COVID-19 pandemic. Why should it be Ex Vivo?

INTRODUCTION: Developing a safe and efficacious vaccine that can induce broad and long-term immunity for SARS-CoV-2 infection is the most critical research to date. As the most potent APCs, dendritic cells (DCs) can induce a robust T cell immunity. In addition, DCs also play an essential role in COVID-19 pathogenesis, making them a potential vaccination target. However, the DCs-based vaccine with ex vivo loading has not yet been explored for COVID-19. AREAS COVERED: This review aims to provide the rationale for developing a DCs-based vaccine with ex vivo loading of SARS-CoV-2 antigen. Here, we discuss the role of DCs in immunity and the effect of SARS-CoV-2 infection on DCs. Then, we propose the mechanism of the DCs-based vaccine in inducing immunity and highlight the benefits of ex vivo loading of antigen. EXPERT OPINION: We make the case that an ex vivo loaded DC-based vaccination is appropriate for COVID-19 prevention.

Necrosis Factor-α (TNF-α) and the Presence of Macrophage M2 and T Regulatory Cells in Nasopharyngeal Carcinoma.

OBJECTIVE: To investigate the correlation between TLR3 and pro-inflammatory cytokines (TNFα, IL6) expression with the distribution of macrophage M2 and Treg on Epstein Barr virus-encoded RNAs (EBER+) nasopharyngeal carcinoma (NPC) tissues. METHODS: A total of 23 FFPE NPC tissue samples were obtained from patients in Dr. Sardjito General Hospital, Yogyakarta, Indonesia in 2008-2010, which expressed EBER was collected. The expressions of TLR3, TNFα, and IL6 were examined using immunofluorescence assay. The distribution of macrophage M2 and Treg were examined by immunohistochemistry with anti-CD163 and -FOXP3 antibodies, respectively. The quantification of fluorescence intensity was analyzed by the RGB space method using ImageJ software. The M2 interpretation was done by the eyeballing method and the M2 scores were divided into 0 (negative), 1 (scant), 2 (focal), 3 (abundant). The average number of Treg FOXP3+ cells in five high power fields was counted. The relationship between variables were tested by the Spearman correlation test, and the coefficient correlation was used to see the correlation between variables. RESULTS: All EBER+ NPC specimens showed TLR3 expression intracellularly. The expression of TNFα could be observed in the cell membranes and secreted extracellularly, while IL6 was secreted to the extracellular area. The expression of TNFα was two times higher than IL6. Most specimens showed low M2 score (56.52%) and high Treg (52.17%). A positive correlation was found between TLR3 and IL6 (12.9%). TNFα was positively correlated with the M2 distribution of 13.7% and Treg distribution of 12.9%, while the rest were explained by other factors. CONCLUSION: TNFα has a positive correlation with M2 and Treg distribution,but mostly through a different mechanism other than EBER-TLR3 interaction. Possibly, other pro-inflammatory and anti-inflammatory cytokines are involved in the formation of the NPC microenvironment, especially related to the presence of M2 and Treg, which provide immunosuppressive effects in NPC tumors. 
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