CAR-T Cell Therapy Summarized
Chimeric antigen receptor (CAR)-T cell therapy to treat B cell malignancies is one of the current, most successful applications of pioneering technology that enables manipulation of specific immune cell types in order to treat disease.
A chimeric antigen receptor is an engineered fusion protein. The extracellular targeting domain is derived from a single-chain fragment variable (scFv) from a monoclonal antibody, and enables the CAR-T cell to recognize and bind to the antigen on the cancer cell. A hinge or spacer peptide and a transmembrane domain provide the link to the intracellular part. This is made up of one or more domains from T cell receptor intracellular signaling and co-stimulatory molecules, and provides a signal to stimulate T cell activation. Gene transfer technology is used to reprogram T cells taken from a patient or donor to express CARs. Following successful transduction, expansion, and infusion into the patient, these engineered CAR-T cells proliferate and specifically target and induce the killing of tumor cells, with the purpose of controlling and eliminating the cancer.
Development, validation, and implementation of robust and accurate bioanalytical methods are vital to monitor the persistence of CAR-T cells and test their safety and efficacy. During CAR-T cell therapy, the initial dose is low, followed by in vivo cell expansion and decline. Bioanalytical assays need to ascertain whether the transferred cells survive, express the appropriate markers, and expand in vivo. Specificity, selectivity, and sensitivity requirements influence the technology platforms selected, and a secure supply of well-characterized reagents over the lifetime of the study is critical to success.
