A CAR combines the binding portions of a monoclonal antibody (scFv) with segments of proteins involved in the signaling machinery of T cells, including CD3ζ, and usually 1 or more additional costimulatory domains, such as CD28 and 4-1BB. When expressed on the surface of T cells, a CAR allows for the direct binding of the immune cells to tumors expressing an antigen of interest on their surface, such as CD30. This recognition bypasses the native requirement for antigen processing and HLA restriction, making a CAR a universal receptor for a particular tumor antigen, thus greatly simplifying the production of cellular immune therapies. The CD30-CARs that have been used in clinical trials conducted at different centers have distinct structures, as illustrated in the figure, and are introduced into autologous T cells using variable methodologies.