For many pathologies such as cancer or neurological disorders, it has been found that Histone Deacetylase (HDAC) activity is disrupted, making them promising targets for drug development. Scientists need access to a broade range of products ( Active Enzyme, inhibitors/activators, Biochemical screening assays…), to simplify their research and identification of HDAC inhibitors.
AIM Biochips – 3D cell culture platform for Immunotherapy and T Cell therapy studies
As mentioned in a previous post  the DAX Biochips from AIM Biotech are an innovative and versatile microfluidic platform, allowing researchers to more easily develop 3D cell culture models, to work as close as possible to what occurs in the human body, but under in-vitro conditions.
Due to its innovative structure (as seen in this general AIM Chips flyer), a broad range of applications have already been validated on this model (Cellular Migration-Invasion Analysis / Angiogenesis studies / Metstasis Modeling System), but what’s new is that now Immunotherapy and T-Cell Therapy studies can be performed on this technology.
TIGIT – Promising target to restore immune response
TIGIT:CD155/CD112 immune inhibition (in green)
Over the last several years, the Immune System has appeared as a central, priority target to fight cancer and various other diseases. Currently, in cancer treatment most of the Immunotherapeutic successes, are molecules developed to modulate and restore immune response by targeting critical Immune Checkpoints.
Some of them can activate T Cells, and on the opposite, some can inhibit this response against cancer cells, such as PD-1 and CTLA4, two of the most studied Immune Checkpoints. The majority of the popular molecules approved in Immunotherapy which have led to clinical benefits, are antibodies inhibiting immune checkpoint activities, such for PD1 with nivolumab and pembrolizumab, or CTLA4 with ipilumab.
IDO/TDO enzymatic pathway as an additional target for Cancer Drug Discovery
BPS Bioscience’s full range of products are available through tebu-bio in Europe.
As a regulator of the immune system, Immune checkpoints appear to be privileged targets In Drug Discovery and Immunotherapy research. Â 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…]
Immunotherapy research: Easily build your own reporter cell line
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…]
Six new reporter cellular lines for Immune checkpoint drug discovery
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.
New Reporter cell lines for Drug discovery and Immunotherapy checkpoint research
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…]
Two top ways to success with knock-out
In March 2016, Mark J Osborn et al published in Molecular Therapy a major article for genome editing (doi:10.1038/mt.2015.197), about knock-out of CD3 in human T-cells. The goal is to improve T-cell-based immunotherapies to fight tumours using engineered allogenic T-cells from healthy donors. It is a very good example of how CRISPR-CAS9 can help medecine. And even if you are not very comfortable with CAR T-cells and the treatments of malignancies, I would recommend you read it and especially take a look at figure 2. Indeed, dear friends of genome editing, the authors made a clear and fair comparison of several KO strategies, covering all the main options. Thus, it is not only a major step for anti-tumour treatments but it is also an excellent overview that reveals the best approaches. So, before reading this post any further, you might like to read the article mentioned above. [Read more…]
IL-17A pathway – a key target for immunotherapies
Fig 1: Function of IL-17 in diverse processes
Interleukin-17 (IL-17) is a family of 6 closely related cytokines, designated IL-17A-F, that play a central role in mediating inflammation, autoimmunity, and host defense. IL-17 is mainly secreted by a specific subset of T helper cells known as TH17 cells (for an overview see Fig 1). The IL-17 cytokines mediate their biological functions via surface receptors on target cells. IL-17A binds to IL-17 receptor A (IL-17RA), which stimulates the production of other pro-inflammatory cytokines including IL-6 and IL-8. IL-17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. IL-17 signaling is also involved in mucosal immunity and host defense against extracellular bacterial and fungal infections (Staph, Candida, Pneumonia, etc.). [Read more…]
Conformational antibody array for mAb process & formulation development
A recent publication by ArrayBridge, Inc., in cooperation with Wayne State University, focuses on monoclonal antibody (mAb) Higher Order Structure Analysis.
The clinical and biological properties of protein-based therapeutics, or biologics, are closely related to their Higher Order Structures (HOS), which in turn can be altered by many physical and chemical conditions. The paper describes a novel technology to monitor changes in mAb HOS – the Protein Conformational Array (PCA) ELISA – which is based on a unique bank of more than 30 well-characterized antibodies enabling the measurement of protein epitope change on the surface of the mAb. [Read more…]