Immune checkpoint molecules play an important role in T cell functionality after TCR/MHC signalling. Blockade of two B7/CD28 family checkpoint molecules, CTLA-4 and PD-1, have already demonstrated excellent efficacy in increasing T cell responses to a variety of tumours. Identification of novel target and new checkpoint blockade remains a key element in Drug Discovery (See “Drug discovery: Immunotherapy checkpoint research for new Cancer treatments“). In this post, let’s take a look at the “Quantibody® Human Immune Checkpoint Molecule Array 1” for the detection of 10 Human Immune Checkpoint biomarkers.
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.
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 research suggests that dendritic cells produce and release CTLA-4, which typically inhibits anticancer responses.
Cancer immunotherapy strategies have made it increasingly evident that the immune system plays an integral role in managing and destroying cancer. Nevertheless, many mechanisms of immune suppression exist that may inhibit antitumour immunity. Recently, strategies that implement antibodies directed against negative immunologic regulators have demonstrated significant success. Cytotoxic T-lymphocyte-associate protein-4 (CTLA-4) was the first immunologic checkpoint to be clinically targeted, by the cancer immunotherapeutic ipilimumab, an FDA-approved drug to treat melanoma. After T-cell activation, CTLA-4 is upregulated on the cell surface where it functions to downregulate T cell function. Ipilimumab binds to CTLA-4 on T cells, which blocks the inhibitory signals and enhances anti-cancer immune responses.
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