Schematic overview of CAR-T cell engineering strategies and recent innovations. The figure is divided into two main parts. Panel (A) shows various chimeric antigen receptor (CAR) T cell constructs, including UNIVERSAL CAR, DUAL CAR, SUPRA CAR, and Tandem CAR designs, highlighting structural modifications aimed at enhancing therapeutic specificity and efficacy. Additionally, non-design-based modifications, such as the incorporation of enzymes like heparanase or catalase, are shown as strategies to improve CAR-T cell performance. Panel (B) explores approaches driven by external stimuli, such as light, ultrasound, or small molecules (e.g., resveratrol, AP1903). The figure also highlights cutting-edge developments, including the use of synthetic nanomaterials and nanovesicles, which represent emerging tools to further refine CAR-T cell therapy, enhancing its safety and effectiveness in clinical applications. (scFv, single-chain variable fragment; FITC, fluorescein isothiocyanate; zipFv, tumour-targeting scFv adaptor; CCR4, C-C chemokine receptor type 4; CXCR3, C-X-C motif chemokine receptor type 3). Created in BioRender. Mazza, M. (2024), https://BioRender.com/p17t758 (accessed on 5 November 2024).