Research Techniques Made Simple: CAR T-Cell Therapy

Abstract

Chimeric antigen receptor (CAR) and chimeric autoantibody receptor T-cell therapy hold great promise in the treatment of cancer and autoimmune disease, respectively. This powerful technique involves genetically engineering T lymphocytes to enable selective destruction of disease-causing cells. In the current approach, a patient's T cells are genetically engineered to express an antigen-specific antibody fragment fused to activating cytoplasmic T-cell signaling domains. After ex vivo activation and genetic modification of a patient's own T cells, the individually tailored CAR T cells are then infused into the patient for the selective destruction of cells bearing the targeted antigen. CAR T cells directed against the CD19 antigen expressed on B lymphoma cells have shown remarkable clinical efficacy in the treatment of refractory lymphoma, with two anti-CD19 CAR-T products recently gaining approval from the US Food and Drug Administration. For dermatological disease, preliminary studies have shown efficacy of CAR T cells in targeting melanoma cells and the pathogenic B cells in pemphigus vulgaris. Despite its great promise, current clinical CAR T-cell (or CAR-T) therapy carries a high risk of cytokine release syndrome, a potentially fatal systemic inflammatory response that can be manifest in cutaneous findings. For the dermatologist, the rapid clinical emergence of CAR-T therapy promises to treat and cure a variety of dermatological conditions, but it also requires an astute awareness of potential cutaneous complications in the increasing number of patients undergoing CAR-T therapy.