Future of Chimeric Antigen Receptors (Cars): Could it Drive Solutions Beyond Cancer? Examples in Autoimmune Diseases

Abstract

MOJ Immunol 2017, 5(3): 00158 vector). After collecting T-cells, usually from patient’s blood (leukoapheresis), they are ex-vivo modified by introducing CAR and by inducing its expression on the T-cell surface. After expanding these CAR+ T-cells, these cells are infused in the bloodstream of the patient to generate a specific immune response against tumour. CART cells become able to recognize cancerous cells through the specificity of a scFv (single-chain variable fragment) to detect an antigen on the surface of the tumour cells, and after that to kill them [2,3]. The affinity and the avidity of the interaction between a CAR and its ligand are higher than the interaction between T cell receptor (TCR) and its peptide-MHC ligand; however, a CAR (instead of TCRs) is unable to recognize intracellular molecules [4]. CAR consists of the combination of a scFv sequence, a transmembrane region and (usually at least two) domains activating for T-cells, such as signalling domains of CD3, CD28 and/or CD137 [5]. Although most of clinical trials are focused on refractory B cell lymphoprolipherative disorders, the CAR strategy is also being relied upon solid tumours. In any case the employment of CARs is not restricted to cancer therapy. A variety of CARs have been used to treat different pathologies such as viral or fungal infections [6] and autoimmune diseases, the main aspect reviewed in this article.