scholarly journals Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Takashi Nakamura ◽  
Moeka Kuroi ◽  
Yuki Fujiwara ◽  
Shota Warashina ◽  
Yusuke Sato ◽  
...  
2014 ◽  
Vol 1840 (6) ◽  
pp. 1892-1901 ◽  
Author(s):  
Youko Fukata ◽  
Aiko Itoh ◽  
Yasuhiro Nonaka ◽  
Takashi Ogawa ◽  
Takanori Nakamura ◽  
...  

Immunobiology ◽  
2013 ◽  
Vol 218 (10) ◽  
pp. 1248-1255 ◽  
Author(s):  
Lena Bundscherer ◽  
Kristian Wende ◽  
Katja Ottmüller ◽  
Annemarie Barton ◽  
Anke Schmidt ◽  
...  

2019 ◽  
Vol 10 (7) ◽  
pp. 2001-2005 ◽  
Author(s):  
M. Braner ◽  
N. Koller ◽  
J. Knauer ◽  
V. Herbring ◽  
S. Hank ◽  
...  

By designing and engineering photo-conditional viral inhibitors, spatiotemporal control of the transporter associated with antigen processing TAP was sustained, allowing the on-demand antigen translocation in human immune cell lines and primary cells by light.


Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 230
Author(s):  
Barbara Costa ◽  
Michael N.C. Fletcher ◽  
Pavle Boskovic ◽  
Ekaterina L. Ivanova ◽  
Tanja Eisemann ◽  
...  

Glioblastomas (GBM) are the most aggressive tumors affecting the central nervous system in adults, causing death within, on average, 15 months after diagnosis. Immunocompetent in-vivo models that closely mirror human GBM are urgently needed for deciphering glioma biology and for the development of effective treatment options. The murine GBM cell lines currently available for engraftment in immunocompetent mice are not only exiguous but also inadequate in representing prominent characteristics of human GBM such as infiltrative behavior, necrotic areas, and pronounced tumor heterogeneity. Therefore, we generated a set of glioblastoma cell lines by repeated in vivo passaging of cells isolated from a neural stem cell-specific Pten/p53 double-knockout genetic mouse brain tumor model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts, they formed high-grade gliomas that faithfully recapitulated the histopathological features, invasiveness and immune cell infiltration characteristic of human glioblastoma. These features make our cell lines unique and useful tools to study multiple aspects of glioblastoma pathomechanism and to test novel treatments in an intact immune microenvironment.


Cell ◽  
2018 ◽  
Vol 175 (6) ◽  
pp. 1701-1715.e16 ◽  
Author(s):  
Benjamin J. Schmiedel ◽  
Divya Singh ◽  
Ariel Madrigal ◽  
Alan G. Valdovino-Gonzalez ◽  
Brandie M. White ◽  
...  

2020 ◽  
Author(s):  
Tatyana Dobreva ◽  
David Brown ◽  
Jong Hwee Park ◽  
Matt Thomson

AbstractAn individual’s immune system is driven by both genetic and environmental factors that vary over time. To better understand the temporal and inter-individual variability of gene expression within distinct immune cell types, we developed a platform that leverages multiplexed single-cell sequencing and out-of-clinic capillary blood extraction to enable simplified, cost-effective profiling of the human immune system across people and time at single-cell resolution. Using the platform, we detect widespread differences in cell type-specific gene expression between subjects that are stable over multiple days.SummaryIncreasing evidence implicates the immune system in an overwhelming number of diseases, and distinct cell types play specific roles in their pathogenesis.1,2 Studies of peripheral blood have uncovered a wealth of associations between gene expression, environmental factors, disease risk, and therapeutic efficacy.4 For example, in rheumatoid arthritis, multiple mechanistic paths have been found that lead to disease, and gene expression of specific immune cell types can be used as a predictor of therapeutic non-response.12 Furthermore, vaccines, drugs, and chemotherapy have been shown to yield different efficacy based on time of administration, and such findings have been linked to the time-dependence of gene expression in downstream pathways.21,22,23 However, human immune studies of gene expression between individuals and across time remain limited to a few cell types or time points per subject, constraining our understanding of how networks of heterogeneous cells making up each individual’s immune system respond to adverse events and change over time.


Author(s):  
Tadepally Lakshmikanth ◽  
Sayyed Auwn Muhammad ◽  
Axel Olin ◽  
Yang Chen ◽  
Jaromir Mikes ◽  
...  

SUMMARYThe human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components, and the inference of global regulatory principles. Here we present a longitudinal, systems-level analysis in 99 healthy adults, 50 to 65 years of age and sampled every 3rd month during one year. We describe the structure of inter-individual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited markers of poor metabolic health suggestive of a functional link between metabolic and immunologic homeostatic regulation.HIGHLIGHTSLongitudinal variation in immune cell composition during one yearInter-individual variation can be described along a principal curveImmune cell and protein relationships are inferredVariability over time is an individual feature correlating with markers of poor metabolic health


2019 ◽  
Author(s):  
Wenfa Ng

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.


Sign in / Sign up

Export Citation Format

Share Document