scholarly journals RNA-Based Vaccines in Cancer Immunotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Megan A. McNamara ◽  
Smita K. Nair ◽  
Eda K. Holl
Keyword(s):  
Immune Response ◽  
Cancer Immunotherapy ◽  
Rna Structure ◽  
Messenger Rna ◽  
Host Cells ◽  
Translational Efficiency ◽  
Tumor Associated Antigen ◽  
Antigen Presenting ◽  
Template Dna

RNA vaccines traditionally consist of messenger RNA synthesized byin vitrotranscription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

Tissue specificity of type I collagen gene expression is determined at both transcriptional and post-transcriptional levels

1984 ◽  
Vol 4 (9) ◽  
pp. 1843-1852
Author(s):  
R J Focht ◽  
S L Adams
Keyword(s):  
Gene Expression ◽  
Rna Structure ◽  
Type I Collagen ◽  
Translational Efficiency ◽  
Type I ◽  
Collagen Gene ◽  
Differentiated Cells ◽  
Collagen Gene Expression

We analyzed the control of type I collagen synthesis in four kinds of differentiated cells from chicken embryos which synthesize very different amounts of the protein. Tendon, skin, and smooth muscle cells were found to have identical amounts of type I collagen RNAs; however, the RNAs had inherently different translatabilities, which were observed both in vivo and in vitro. Chondrocytes also had substantial amounts of type I collagen RNAs, even though they directed no detectable synthesis of the protein either in vivo or in vitro. Type I collagen RNAs in chondrocytes display altered electrophoretic mobilities, suggesting that in these cells the reduction in translational efficiency may be mediated in part by changes in the RNA structure. These data indicate that control of type I collagen gene expression is a complex process which is exerted at both transcriptional and post-transcriptional levels.

scholarly journals Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 364 ◽  
Author(s):  
Itziar Gómez-Aguado ◽  
Julen Rodríguez-Castejón ◽  
Mónica Vicente-Pascual ◽  
Alicia Rodríguez-Gascón ◽  
María Ángeles Solinís ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plasmid Dna ◽  
Messenger Rna ◽  
Insertional Mutagenesis ◽  
Gene Editing ◽  
State Of The Art ◽  
Translational Efficiency ◽  
Future Perspectives ◽  
Therapeutic Tool

The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.

scholarly journals Development of a Secondary Immune Response toMycobacterium tuberculosisIs Independent of Toll-Like Receptor 2

2010 ◽  
Vol 79 (3) ◽  
pp. 1118-1123 ◽  
Author(s):  
Amanda McBride ◽  
Kamlesh Bhatt ◽  
Padmini Salgame
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Host Resistance ◽  
Toll Like Receptor ◽  
Response Phenotype ◽  
Toll Like Receptor 2 ◽  
Antigen Presenting ◽  
Memory Immune Response

ABSTRACTPublished work indicates that the contribution of Toll-like receptor 2 (TLR2) to host resistance during acuteMycobacterium tuberculosisinfection is marginal. However, in these studies, TLR2 participation in the memory immune response toM. tuberculosiswas not determined. The substantialin vitroevidence thatM. tuberculosisstrongly triggers TLR2 on dendritic cells and macrophages to bring about either activation or inhibition of antigen-presenting cell (APC) functions, along with accumulating evidence that memory T cell development can be calibrated by TLR signals, led us to question the role of TLR2 in host resistance to secondary challenge withM. tuberculosis. To address this question, a memory immunity model was employed, and the response of TLR2-deficient (TLR2 knockout [TLR2KO]) mice following a secondary exposure toM. tuberculosiswas compared to that of wild-type (WT) mice based on assessment of the bacterial burden, recall response, phenotype of recruited T cells, and granulomatous response. We found that upon rechallenge withM. tuberculosis, both WT and TLR2KO immune mice displayed similarly enhanced resistance to infection in comparison to their naïve counterparts. The frequencies ofM. tuberculosis-specific gamma interferon (IFN-γ)-producing T cells, the phenotypes of recruited T cells, and the granulomatous responses were also similar between WT and TLR2KO immune mice. Together, the findings from this study indicate that TLR2 signaling does not influence memory immunity toM. tuberculosis.

Nitrosylation of Platelet MHC Class I Molecules Directs Their Movement into the Immunosuppressive MHC Class I Processing Pathway within Antigen Presenting Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 837-837
Author(s):  
John W. Semple ◽  
Edwin R. Speck ◽  
John Freedman
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Brefeldin A ◽  
Antigen Presenting Cells ◽  
Class I ◽  
Antigen Presenting ◽  
Platelet Transfusions

Abstract Previous studies have demonstrated that recipient mice require the production of nitric oxide (NO) within their antigen presenting cells (APC) in order to generate IgG anti-donor immunity against allogeneic platelet transfusions. NO has a complex biochemistry and several of its conjurors could be involved in this response; the most obvious is peroxynitrite (ONOO-) generated by the spontaneous combination of NO and superoxide (O2•−). ONOO- is a potent oxidant that can spontaneously nitrosylate lysine and tyrosine residues in proteins within the phagolysosome. To address the role of ONOO- in platelet immunity, we transfused GP91 PHOX knockout mice that lack the ability to produce O2•− and thus ONOO-. Results show that when wild type C57BL/6 mice were transfused with allogeneic BALB/c platelets, they developed a weak IgG anti-donor antibody response by the fifth transfusion. In contrast, PHOX KO mice generated IgG anti-donor antibodies by the 2nd transfusion and their IgG anti-donor antibody titres were significantly higher than the WT recipients. This suggested that ONOO- and protein nitrosylation may be linked with an immunosuppressive event within the recipient. This was confirmed by demonstrating that in vitro nitrosylation of platelet antigens with the ONOO- donor SIN-1 inhibited the ability of the platelets to mount an IgG immune response when transfused into allogeneic recipients. Nitrosylated platelet antigen trafficking within recipient APC was assessed by using adherent macrophages and various inhibitors of processing. When adherent APC were pulsed with nitrosylated platelet antigens in the presence of either Brefeldin A or proteosome inhibitors, IgG anti-platelet immunity against the platelets was restored. Furthermore, the IgG immunity could also be rescued against the nitrsosylated platelets if the recipients were first depleted of CD8+ T cells by injection of a monoclonal antibody. These results suggest that if platelet antigens are nitrosylated within antigen presenting cells, they are preferentially shunted to the MHC class I processing pathway and presented to CD8+ T cells that suppress the IgG immune response. Thus, it appears that reactive oxygen species act as intracellular regulators that determine whether a productive IgG immune response against platelet transfusions will occur.

Photodynamic Therapy in Combination with Sorafenib for Enhanced Immunotherapy of Lung Cancer

2020 ◽  
Vol 16 (8) ◽  
pp. 1219-1228
Author(s):  
Tianxing Guo ◽  
Weiwei Lin ◽  
Wenshu Chen ◽  
Yanyun Huang ◽  
Lihuan Zhu ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Therapy ◽  
Cancer Immunotherapy ◽  
Immunogenic Cell Death ◽  
Strong Inhibition ◽  
Novel Approach ◽  
Great Progress ◽  
A Cell

The emerging of cancer immunotherapy is a great progress in cancer therapy. However, accumulating evidences have shown that tumor microenvironment (TME) exerted strong inhibition effects on cancer immunotherapy. In order to solve this issue, a cell membrane vehicle (CMV) was developed and employed to encapsulate both chlorins e6 (Ce6) and sorafenib (Sfn). The obtained drug delivery system (DDS, CMV/C-S was expected to enhance the immune response in cancer therapy by remodeling the TME. The results showed that CMV/C-S was highly stable under physiological environment with responsive drug release upon laser irradiations and high tumor targetability, which all contributed to promising anticancer performance in vitro / in vivo. Especially, the photodynamic nature of Ce6 could exert significant immunogenic cell death (ICD) to trigger immune response. At the same time, with the TME regulation effects of Sfn, the outcome of cancer immunotherapy was significantly enhanced as compare to mono-therapies. The study offers a novel approach for effective cancer immunotherapy.

scholarly journals Different innate immunity and clearance of Salmonella Pullorum in macrophages from White Leghorn and Tibetan Chickens

2018 ◽  
Vol 16 ◽  
pp. 205873921878003 ◽  
Author(s):  
Shao Wei ◽  
Keliang Wu ◽  
Yijuan Nie ◽  
Xiang Li ◽  
Zhengxing Lian ◽  
...  
Keyword(s):  
Immune Response ◽  
Interleukin 10 ◽  
Host Cells ◽  
Blood Monocytes ◽  
White Leghorn ◽  
Inflammatory Protein ◽  
Crucial Effect ◽  
Salmonella Pullorum ◽  
Macrophage Inflammatory Protein

Salmonella enterica serovar Gallinarum biovar Pullorum ( S. Pullorum) is responsible for the systemic salmonellosis in different breeds of chickens. Macrophages, as host cells, play a key role in the innate immune response following infection with S. Pullorum. In this study, we first generated macrophages from two breeds of chicken (White Leghorn (WL) and Tibetan Chickens (TC)) peripheral blood monocytes in vitro. Then, we showed that the production of interleukin-1β (IL-1β), macrophage inflammatory protein-1β (MIP-1β) and interleukin-10 (IL-10) in lipopolysaccharide (LPS)-treated macrophages was significantly higher compared with the unstimulated cells in TC. LPS triggered only more expression of IL-10 in WL macrophages. Furthermore, macrophages from TC eliminated intracellular bacteria more efficiently than those from WL after S. Pullorum infection at a multiplicity of infection (MOI) 1. In addition, the variation between individuals and sex had the crucial effect on the immune response to LPS and S. Pullorum invasion.

scholarly journals Tissue specificity of type I collagen gene expression is determined at both transcriptional and post-transcriptional levels.

1984 ◽  
Vol 4 (9) ◽  
pp. 1843-1852 ◽  
Author(s):  
R J Focht ◽  
S L Adams
Keyword(s):  
Gene Expression ◽  
Rna Structure ◽  
Type I Collagen ◽  
Translational Efficiency ◽  
Type I ◽  
Collagen Gene ◽  
Differentiated Cells ◽  
Collagen Gene Expression

We analyzed the control of type I collagen synthesis in four kinds of differentiated cells from chicken embryos which synthesize very different amounts of the protein. Tendon, skin, and smooth muscle cells were found to have identical amounts of type I collagen RNAs; however, the RNAs had inherently different translatabilities, which were observed both in vivo and in vitro. Chondrocytes also had substantial amounts of type I collagen RNAs, even though they directed no detectable synthesis of the protein either in vivo or in vitro. Type I collagen RNAs in chondrocytes display altered electrophoretic mobilities, suggesting that in these cells the reduction in translational efficiency may be mediated in part by changes in the RNA structure. These data indicate that control of type I collagen gene expression is a complex process which is exerted at both transcriptional and post-transcriptional levels.

scholarly journals SPECIFIC PROTEIN SYNTHESIS IN CELLULAR DIFFERENTIATION

1972 ◽  
Vol 55 (3) ◽  
pp. 653-680 ◽  
Author(s):  
M. Paul ◽  
M. R. Goldsmith ◽  
J. R. Hunsley ◽  
F. C. Kafatos
Keyword(s):  
Protein Synthesis ◽  
Messenger Rna ◽  
Developmental Stages ◽  
Specific Protein ◽  
Chain Elongation ◽  
Synthetic Activity ◽  
Translational Efficiency ◽  
Kinetics Of

Silkmoth follicles, arranged in a precise developmental sequence within the ovariole, yield pure and uniform populations of follicular epithelial cells highly differentiated for synthesis of the proteinaceous eggshell (chorion). These cells can be maintained and labeled efficiently in organ culture; their in vitro (and cell free) protein synthetic activity reflects their activity in vivo. During differentiation the cells undergo dramatic changes in protein synthesis. For 2 days the cells are devoted almost exclusively to production of distinctive chorion proteins of low molecular weight and of unusual amino acid composition. Each protein has its own characteristic developmental kinetics of synthesis. Each is synthesized as a separate polypeptide, apparently on monocistronic messenger RNA (mRNA), and thus reflects the expression of a distinct gene. The rapid changes in this tissue do not result from corresponding changes in translational efficiency. Thus, the peptide chain elongation rate is comparable for chorion and for proteins synthesized at earlier developmental stages (1.3–1.9 amino acids/sec); moreover, the spacing of ribosomes on chorion mRNA (30–37 codons per ribosome) is similar to that encountered in other eukaryotic systems.

scholarly journals The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response

2016 ◽  
Vol 84 (12) ◽  
pp. 3458-3470 ◽  
Author(s):  
Mike Khan ◽  
Jerome S. Harms ◽  
Fernanda M. Marim ◽  
Leah Armon ◽  
Cherisse L. Hall ◽  
...  
Keyword(s):  
Immune Response ◽  
Second Messenger ◽  
Host Immune Response ◽  
Vital Role ◽  
Host Cells ◽  
Content Type ◽  
Type Iv

Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host- Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a Δ bpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the Δ bpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase Δ cgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, Δ bpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection.

scholarly journals Swine Dendritic Cell Response to Porcine Reproductive and Respiratory Syndrome Virus: An Update

2021 ◽  
Vol 12 ◽  
Author(s):  
Jesús Hernández ◽  
Yanli Li ◽  
Enric Mateu
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Respiratory Pathogen ◽  
Respiratory Syndrome Virus ◽  
Adaptive Immune ◽  
Unexplored Area ◽  
Plasmacytoid Dcs ◽  
Antigen Presenting

Dendritic cells (DCs) are the most potent antigen-presenting cells, unique to initiate and coordinate the adaptive immune response. In pigs, conventional DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte-derived DCs (moDCs) have been described in blood and tissues. Different pathogens, such as viruses, could infect these cells, and in some cases, compromise their response. The understanding of the interaction between DCs and viruses is critical to comprehend viral immunopathological responses. Porcine reproductive and respiratory syndrome virus (PRRSV) is the most important respiratory pathogen in the global pig population. Different reports support the notion that PRRSV modulates pig immune response in addition to their genetic and antigenic variability. The interaction of PRRSV with DCs is a mostly unexplored area with conflicting results and lots of uncertainties. Among the scarce certainties, cDCs and pDCs are refractory to PRRSV infection in contrast to moDCs. Additionally, response of DCs to PRRSV can be different depending on the type of DCs and maybe is related to the virulence of the viral isolate. The precise impact of this virus-DC interaction upon the development of the specific immune response is not fully elucidated. The present review briefly summarizes and discusses the previous studies on the interaction of in vitro derived bone marrow (bm)- and moDCs, and in vivo isolated cDCs, pDCs, and moDCs with PRRSV1 and 2.

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