Fig. 1.

Schematic illustration of the endogenous T‑cell receptor (TCR) and chimeric antigen receptor (CAR) constructs. Malignant cells present tumoral antigens via major histocompatibility (MHC) molecules that are recognized by the endogenous TCR. CAR T‑cells recognize targeted surface antigens (e. g., CD19) via their ligand binding domain derived from a monoclonal antibody (V_H and V_L; variable heavy and light chain). The antigen recognition moiety is linked to a transmembrane domain with a hinge fragment. All CAR constructs contain the CD3ζ signaling domain. Second or later generation CARs further contain one or more co-stimulatory domains (e. g., CD28 or 4‑1BB), enhancing the cytotoxic response of the transfected cell upon antigen recognition. T cells redirected for universal cell killing (TRUCKs) release cytokines or express co-stimulatory ligands upon antigen stimulation with the intent to augment activation and to attract cells of the innate immune system. Adapted from [2]