scholarly journals CpG Oligodeoxynucleotide Developed For Activating Primate Immune Responses Promotes Anti-Tumoral Effect Combine With Neo-Antigen Based mRNA Cancer Vaccine

2021 ◽  
Author(s):  
Rongkuan Hu ◽  
Qin Li ◽  
Jie Ren ◽  
Wei Liu ◽  
Guoqin Jiang
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Cancer Vaccines ◽  
Cytokine Production ◽  
Toll Like Receptor ◽  
Human Pbmc ◽  
Cpg Oligodeoxynucleotides ◽  
Adaptive Immune ◽  
Cpg Oligodeoxynucleotide

Abstract Synthetic phosphorthiolate modified CPG-oligodeoxynucleotides (CPG-ODN) activate innate and adaptive immune responses, which being exploited as a therapeutic approach. Here, we first screened and identified a new CpG-B class ODN (CpG2018B) that effectively stimulates type II interferon both in mouse Plasmacytoid dendritic cells (p-DC) and human PBMC. In addition, CpG2018B promotes cytokine production mainly via toll-like receptor 9 (TLR9) pathways. We further demonstrated that intratumoral (IT) injection of CpG2018B inhibits melanoma growth in syngeneic models and could turn “cold” tumors into “hot” tumors. Then, CpG2018B and mRNA based neo-antigen cancer vaccine were encapsulated into lipid-nanoparticle (LNP) and intratumoral injected into melanoma mice models. Interestingly, vaccination with CpG or mRNA vaccine alone could inhibit tumor growth respectively, while, CpG combine with mRNA vaccine enhanced the anti-tumor effect. At last, we described the long-term safety and tolerability of CpG2018B and mRNA therapy in mice models. In conclusion, we identified a novel CpG-B ODNs to promote immune response and CpG combine with mRNA cancer vaccines are attractive candidate for immune stimulatory sequences (ISS) based therapeutic strategies.

scholarly journals Immunological effects of different types of synthetic CpG oligodeoxynucleotides on porcine cells

RSC Advances ◽  
2017 ◽  
Vol 7 (68) ◽  
pp. 43289-43299 ◽  
Author(s):  
Ruiqiao Li ◽  
Lilin Zhang ◽  
Peidian Shi ◽  
Hui Deng ◽  
Yi Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
Animal Species ◽  
Toll Like Receptor ◽  
Adaptive Immune Responses ◽  
Cpg Oligodeoxynucleotides ◽  
Adaptive Immune ◽  
Different Types ◽  
Immunological Effects

The agonists of toll-like receptor 9, synthetic oligodeoxynucleotides (ODNs) containing CpG sequences, stimulate innate and adaptive immune responses in humans and a variety of animal species.

scholarly journals Precision N-Glycoproteomic Profiling of Murine Peritoneal Macrophages After Different Stimulations

2021 ◽  
Vol 12 ◽  
Author(s):  
Lujie Yang ◽  
Tianqi Gong ◽  
Huali Shen ◽  
Jiangnan Pei ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Macrophage Activation ◽  
Cytokine Production ◽  
Peritoneal Macrophages ◽  
Biological Processes ◽  
Toll Like Receptor ◽  
Adaptive Immune ◽  
Murine Peritoneal Macrophages ◽  
Molecular Patterns ◽  
Stimulation Of

Macrophages are important immune cells that participate in both innate and adaptive immune responses, such as phagocytosis, recognition of molecular patterns, and activation of the immune response. In this study, murine peritoneal macrophages were isolated and then activated by LPS, HSV and VSV. Integrative proteomic and precision N-glycoproteomic profiling were conducted to assess the underlying macrophage activation. We identified a total of 587 glycoproteins, including 1239 glycopeptides, 526 monosaccharide components, and 8326 intact glycopeptides in glycoproteomics, as well as a total of 4496 proteins identified in proteomic analysis. These glycoproteins are widely involved in important biological processes, such as antigen presentation, cytokine production and glycosylation progression. Under the stimulation of the different pathogens, glycoproteins showed a dramatic change. We found that receptors in the Toll-like receptor pathway, such as Tlr2 and CD14, were increased under LPS and HSV stimulation. Glycosylation of those proteins was proven to influence their subcellular locations.

scholarly journals Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling

2020 ◽  
Vol 217 (8) ◽  
Author(s):  
Thomas Jun Feng Lim ◽  
Maegan Bunjamin ◽  
Christiane Ruedl ◽  
I-hsin Su
Keyword(s):  
Immune Responses ◽  
Cell Activation ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Tolerance Induction ◽  
Direct Interaction ◽  
Toll Like Receptor ◽  
Dendritic Cell Activation ◽  
Dependent Cell ◽  
Draining Lymph Nodes

Talin critically controls integrin-dependent cell migration, but its regulatory role in skin dendritic cells (DCs) during inflammatory responses has not been investigated. Here, we show that talin1 regulates not only integrin-dependent Langerhans cell (LC) migration, but also MyD88-dependent Toll-like receptor (TLR)–stimulated DC activation. Talin1-deficient LCs failed to exit the epidermis, resulting in reduced LC migration to skin-draining lymph nodes (sdLNs) and defective skin tolerance induction, while talin1-deficient dermal DCs unexpectedly accumulated in the dermis despite their actomyosin-dependent migratory capabilities. Furthermore, talin1-deficient DCs exhibited compromised chemotaxis, NFκB activation, and proinflammatory cytokine production. Mechanistically, talin1 was required for the formation of preassembled TLR complexes in DCs at steady state via direct interaction with MyD88 and PIP5K. Local production of PIP2 by PIP5K then recruited TIRAP to the preassembled complexes, which were required for TLR signalosome assembly during DC activation. Thus, talin1 regulates MyD88-dependent TLR signaling pathways in DCs through a novel mechanism with implications for antimicrobial and inflammatory immune responses.

Effective CpG DNA delivery using amphiphilic cycloamylose nanogels

2015 ◽  
Vol 3 (2) ◽  
pp. 256-264 ◽  
Author(s):  
Y. Tahara ◽  
J. Yasuoka ◽  
S. Sawada ◽  
Y. Sasaki ◽  
K. Akiyoshi
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Dna Delivery ◽  
Cell Uptake ◽  
Cpg Dna ◽  
Cpg Oligodeoxynucleotides

Native CpG oligodeoxynucleotides induce inflammatory immune responses through cytokine production by their effective cell uptake with amphiphilic cationic cycloamylose nanogels.

scholarly journals Mathematical model of a personalized neoantigen cancer vaccine and the human immune system

2021 ◽  
Vol 17 (9) ◽  
pp. e1009318
Author(s):  
Marisabel Rodriguez Messan ◽  
Osman N. Yogurtcu ◽  
Joseph R. McGill ◽  
Ujwani Nukala ◽  
Zuben E. Sauna ◽  
...  
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Cancer Vaccine ◽  
Tumor Size ◽  
Cancer Vaccines ◽  
Patient Specific ◽  
Human Immune System ◽  
Human Immune

Cancer vaccines are an important component of the cancer immunotherapy toolkit enhancing immune response to malignant cells by activating CD4+ and CD8+ T cells. Multiple successful clinical applications of cancer vaccines have shown good safety and efficacy. Despite the notable progress, significant challenges remain in obtaining consistent immune responses across heterogeneous patient populations, as well as various cancers. We present a mechanistic mathematical model describing key interactions of a personalized neoantigen cancer vaccine with an individual patient’s immune system. Specifically, the model considers the vaccine concentration of tumor-specific antigen peptides and adjuvant, the patient’s major histocompatibility complexes I and II copy numbers, tumor size, T cells, and antigen presenting cells. We parametrized the model using patient-specific data from a clinical study in which individualized cancer vaccines were used to treat six melanoma patients. Model simulations predicted both immune responses, represented by T cell counts, to the vaccine as well as clinical outcome (determined as change of tumor size). This model, although complex, can be used to describe, simulate, and predict the behavior of the human immune system to a personalized cancer vaccine.

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