Cell-Based ELISA tests now enable precise measurement of the phosphorylation status or expression profiles of target proteins (biomarkers) in whole cells. In this post, a review of high performing cell-based assays is made.
Cell-based assays have become a classic way to monitor cells’ reactions to a treatment or a specific stimulus. They involve a reporter construction and a detection system. The classic system is Firefly Luciferase, combined or not with Renilla Luciferase. Luciferases allow simple data acquisition on a plate reader.
Nevertheless, Firefly Luciferase requires cell lysis. End-point acquisition is the only method and optimizations of the right moment is recommended. To bring more convenience, robustness and higher sensitivity, Gaussian luciferase can well be your better choice. [Read more…]
As a regulator of the immune system, Immune checkpoints appear to be privileged targets In Drug Discovery and Immunotherapy research. Indeed, promising molecules tested in clinical trials and approved are giving new hope for cancer treatment. Beyond checkpoint receptors, the Enzymatic pathway also regulates the immune system and provides additional targets for Drug Development, and may increase the chances of clinical success in Cancer treatment.
In addition to already developed Immune Checkpoint Reporter cell lines (as introduced in my previous post), BPS Bioscience also provide tools to study the enzymatic pathway, such as the tryptophan catabolism pathway controlled by IDO1: The IDO / TDO pathway. [Read more…]
As discussed previously in our recent Drug Discovery post, Immunotherapy is one of the central research fields for various disease treatments and also certain cancers. A major regulator of immune homoeostasis and preventing autoimmunity, but potentially dysregulated in various cancers, Immune Checkpoint targeting has already led to promising treatment molecules (Nivolumab, Pembrolizumab…).
To face the challenges of Immune system complexity and the tumor microenvironment, BPS Biosciences have developed several reporter cellular lines (the full listing is here) to complement Biochemical assays. By providing more physiological outcomes in a cellular context (functionality of the whole cell signaling pathway) BPS cell lines allow, for example, the identification of an agonist vs antagonistic effect of your candidate. [Read more…]
PD-1:PD:-L1 immune checkpoint pathway targeting immunotherapies have shown great potential for many cancer patients. Recently, The FDA has granted accelerated approval to the immunotherapy drug pembrolizumab (Keytruda® – humanized monoclonal IgG4 antibody against human cell surface receptor PD-1) for use in some patients with advanced gastric stomach cancer (see NIH-NCI news). However, response to these treatments is not guaranteed for each patient. With the complexity of the immune system and tumour microenvironment, providing more physiological outcomes for immunotherapies is necessary. Biochemical assays alone cannot consider the functionality of the whole cell signalling pathway. Complementing them with cell-based assays provides a comprehensive approach for identifying and developing new and improved immunotherapy treatments. Cellular line engineering has simplified and accelerated the development of such immunoassays. Targets have been chosen from both immune activators and suppressors with the aim of obtaining precise control of the immune system.
BPS Bioscience have engineered 6 cellular lines, turning them into cell-based reporter assays for Human Immune Checkpoint research. I’d like to present a summary of how each cellular line functions.
In the last few decades, in the field of Drug Discovery, Immunotherapy has gained more and more importance for the treatment of various diseases and in particular for certain types of cancer. Based on inducing, enhancing or suppressing an immune response, this therapeutic manipulation has led to promising clinical results.
Major regulators of Immune activation, Immune checkpoints play a key role in maintaining immune homoeostasis and preventing autoimmunity. However in some cancers, these checkpoints can be used to avoid any activation of the immune response against cancer cells. Immunotherapies based on targeting immune checkpoint pathways in Drug Discovery, have already led to the development of promising molecules (Nivolumab, Pembrolizumab…) tested in clinical trials and approved, which are giving new hope for cancer treatments. [Read more…]
Human Peripheral Blood Mononuclear Cells (hPBMCs) are essential for designing cellular models to be used in cell therapy and drug discovery research programs [1-7, 12]. Being able to access reliable and ethical sources of well-characterized hPBMCs is now becoming fundamental for running physiologically relevant cell-based assays. A good opportunity to discuss the expanding applications for hPBMCs in drug development, that Patricia Bresnahan, PhD (Global Marketing Director at HemaCare Corporation) has observed over the last years.
Which roles do IDO and TDO play in Immunotherapy? Immune evasion is one of the identifying hallmarks of cancer and researchers are investigating the complex mechanisms that enable cancer cells to evade the host’s immune system. In the context of a tumor, Tryptophan (Trp or L-Trp) catabolizing enzymes have been shown to assist cancer cells in immune evasion. [Read more…]
Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated transcription factors of the Nuclear Receptor superfamily. PPAR active compounds are of significant interest in multiple pharmaceutical domains.
In this post, we’ll highlight a clever in vitro experimental approach to screen the PPAR-specific activity of therapeutically significant PPAR agonists or antagonists.
Lipodystrophies are disorders characterized by complete or selective loss of adipose tissue from various regions of the body. They might lead to severe metabolic disorders. The development of reliable cellular experimental models mimicking such diseases in vitro is extremely challenging (1). One of the main hurdle in the design of such in vitro cellular models is the access to reliable sources of well-qualified primary cells and the identification of optimal cell culture conditions.