Recently, BPS Bioscience have released a new Adenosine A2A Receptor (A2AR / ADORA2A) Functional Recombinant Cell Line for screening A2AR agonists and antagonists. An excellent means to efficiently evaluate the Adenosine cell signaling pathway known to be deeply involved in all phases of inflammation and immune responses with potential interest in immunotherapies.
The HiP™ (High Purity) distinction by BPS Bioscience starts, of course (as the name says), with a high purity level. But that’s not enough. Such pure proteins may aggregate, which is not compatible with binding assays. Thus, the HiP™ label also demands a low level of aggregation, or even none at all. [Read more…]
Immunotherapy represents a field in Drug Discovery which is quickly developing and leading to significant progress in treatments of a number of diseases, especially cancer. The approach is based on inducing, enhancing, or surpressing an immune response. Therapeutic manipulation of immunopathways has led to promising clinical results . The first therapeutic antibodies directed against the checkpoint receptor PD-1 have been already brought to the market (Nivolumab, Pembrolizumab) by Bristol Myers Squibb and Merck/MSD respectively, and approved for the treatment of diverse cancer types.
Today, I would like to review tools to build up a comprehensive assay set up for cell based inhibitor screening on PD-1 / PD-L1/PD-L2 binding. [Read more…]
Extracellular adenosine 5′-triphosphate (ATP) is released by dying and damaged cells, and it acts on many immune cells to promote inflammation. On the other hand, the unphosphorylated
metabolite, adenosine, functions as an anti-inflammatory molecule. Two extracellular ecto-5´-Nucleotidases, CD39, and CD73, convert extracellular ATP to ADP/AMP and AMP to adenosine, respectively, leading to elevated levels of extracellular adenosine (Fig 1). [Read more…]
Over the past months, we have released a number of posts introducing inhibitor screening assays intended to investigate immuno checkpoint protein interactions, such as PD-1/PD-L1/PD-L2; B7-1/CD28, B7-1/CTLA4; BLTA/HVEM, CD47/SIRPα; GITR/GITRL and many others – for an overview, you might like to read 9 pathway-specific screening assays in Immunotherapy.
Today, I’d like to concentrate on the TIGIT/CD226 pathway, because it acts through a novel mechanism to regulate CD8+ T cell functions within the tumour microenvironment. [Read more…]
Immune checkpoint molecules play an important role in T cell functionality after TCR/MHC signaling. In fact, blockade of two B7/CD28 family checkpoint molecules, namely CTLA-4 and PD-1, have already demonstrated excellent efficacy in increasing T cell responses to a variety of tumors. [Read more…]
Donor-derived lymphocytes attack a patient’s cancer — but may attack the patient as well. Donor chimeric antigen receptor (CAR) T cells, on the other hand, brought remissions without this troubling complication.
CAR T cells continue to make waves: At the latest annual meeting of the American Association for the Advancement of Science, it was announced that CAR T cells, in which T cells from a patient are genetically reprogrammed to target cancer cells, removed all traces of cancer in the bone marrow of 27 out of 29 acute lymphoblastic leukemia patients. Nineteen of 30 individuals with non-Hodgkin lymphoma also responded in the form of partial or complete responses. The cumulative successes found in CAR T cell studies have labeled them “extraordinary.” [Read more…]
Trpytophan (trp) is an important and essential amino acid that has a variety of functions within the cell. In addition to being incorporated into the polypeptide chain of proteins, various catabolic pathways can produce a number of functional Trp derivatives. Trp is the biosynthetic precursor of the co-factor NAD, a number of antibiotics, and the neurotransmitters serotonin and melatonin.
The factors regulating the fate of Trp in the cell have yet to be fully elucidated, but likely involve specific enzymes that may vary in expression levels or with the cell type (Fig 1 – Shown is a depiction of two important tryptophan catabolic pathways and the enzymes that participate in the process). [Read more…]
Knowledge about which epitopes are recognized by a blocking antibody can help researchers to develop improved antibodies for drug discovery and to better understand the mechanism of inhibition.
The binding of Programmed Cell Death Protein 1 (PD-1), one of the receptors expressed on activated T-cells (see Figure 1), to its ligands PD-L1 and PD-L2, negatively regulates immune responses. PD-1 ligands are found on most cancers, and PD-1:PD-L1/2 interaction inhibits T cell activity and allows cancer cells to escape immune surveillance.
The first therapeutic antibodies in this field have been directed against the checkpoint receptor PD-1 (Nivolumab by Bristol Myers Squibb and Pembrolizumab by Merck/MSD). The drugs have been approved for the treatment of diverse cancer types during the past years. The PD-1:PD-L1/2 pathway is also involved in regulating autoimmune responses, making these proteins promising therapeutic targets for a number of cancers, as well as multiple sclerosis, arthritis, lupus, and type I diabetes. Further research projects in this field are rapidly evolving as scientists seek to identify the next generation of therapies especially developing therapies combining different therapeutic approaches. [Read more…]