The treatment of diseases by inducing, enhancing, or surpressing an immune response is referred to as Immunotherapy. T-cell activation and inactivation requires the coordination of various co-inhibitory and co-stimulatory signals and most immunotherapies modulate these signals.

Therapeutic manipulation of immunopathways has lead to promising clinical results for the treatment of a number of diseases such as cancer, autoimmune diseases and inflammatory diseases. Research in this field is rapidly evolving as scientists seek to identify the next generation of therapies.

In the first post of a series of three,  I will describe the B7-1 : CD28 and B7-1 : CTLA4 pathways and summarize the portfolio of tools currently available to researchers to investigate these pathways. In fact, these are the first kits on the market to screen for inhibitors of these pathways.

In Pharma screening departments there is a strong need for Ca²⁺ measurement methods.

Why is this?

GPCRs (G Protein Coupled Receptors) are still major targets of pharmaceutical screenings.

Around 30-40% of all drugs on the market are directed against GPCRs.

Drugs have an impact on the GPCR activity and thus the downstream signal transduction cascade. GPCRs are linked to the activity of heterotrimeric G proteins which consist of alpha, beta and gamma subunits. These G proteins have an effect on PhosphoLipase C (PLC) which leads to the release of Inositol Phosphate 3 (IP3) which finally leads to intracellular Ca²⁺ mobilization (release from the endoplasmic reticulum ) – Ca²⁺ finally has effect on a number of further cellular processes.

The fact that GPCR activation always leads to Ca²⁺mobilization is commonly used to indirectly measure the impact of compounds/drug candicates on GPCRs.

Hence the need for Ca²⁺ measurement methods, such as the following…

Hepatocytes are commonly used in drug discovery and preclinical drug development to perform experiments requiring intact cellular systems. Intact hepatocytes contain the major hepatic drug-metabolizing enzymes required to study the four categories of xenobiotic biotransformation: Hydrolysis, Reduction, Oxidation and Conjugation. Because of these enzymes, hepatocytes provide a viable and cost-effective alternative to in vivo compound testings.

Live staining astrocytes derived from knock‐in reporter line for GFAP

Somatic cell reprogramming technology enables researchers to build disease models by generating iPSC lines from patient samples, to differentiate them into targeted primary cells, and manifest disease symptoms in vitro.

So far, many disease models for CNS disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Autism, Schizophrenia, and Amyotrophic Lateral Sclerosis (ALS), have been generated using this strategy. However, there is a common limitation for disease models solely based on patient‐derived iPSC lines: the mechanism of action of genetic mutations underlying a disease is often complicated by diverse genetic backgrounds from patient to patient since most genetic mutations associated with CNS disorders have in general small effect on the disease phenotype.