With the development of biotechnology, a type of treatment in which a patient’s T cells (a type of immune system cell) are gene engineered to attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is being studied in the treatment of some types of cancer. Also called chimeric antigen receptor T-cell therapy. Check Emily Whitehead’s amazing cancer fight story with CAR T-cell therapy here.
CAR is mainly composed of a cell membrane extracellular antigen binding region and an intracellular signal transduction region through a hinge region and a transmembrane region. The extracellular antigen binding domain can specifically recognize and bind to a target cell surface antigen. It is derived from a single-chain variable region(scFv) of a monoclonal antibody. The intracellular signal transduction domain is mainly composed of a costimulatory signal and a CD3zeta chain of T cell receptor (TCR). After CAR-T cells binding to the target cell antigen through the scFv, the intracellular signal transduction region transmits signals to the T cell, thereby activates T cell, which in turn results secretion of perforin, granzymes and interferons to kill cancel cell.
The FDA has approved two CAR T-cell therapies in 2018, namely Kymriah of Novartis and Yescarta of Gilead. Both of them are directed against CD19-positive B-cell tumors, using the same antigen-binding region, the scFv derived from the mouse monoclonal antibody FMC63. So our R19M and other detection products are compatible with these established CAR T-Cell therapies.
Generation of CAR-T cell requires transfection of the CAR gene into T cell via a viral or non-viral system. When the CAR is expressed on the membrane of T cell, CAR T-cell then has the activity of recognizing and killing the target cells. Therefore, accurate detection of CAR-positive T cells is a key step in the quality control of CAR T-Cell therapy, and an important criteria in clinical dose control, process monitoring and assistant diagnosis.
There are two common types of detection methods: detection of CAR gene-positive T cells(qPCR) and detection of CAR protein-positive T cells (FACS).
There are several reagents, including anti-mouse IgG (Fab’)2, Protein L, CD19/Fc, and mouse monoclonal antibody 136.20.1.