Abstract
Cancer therapy has entered a new era, transitioning from unspecific chemotherapeutic agents to increasingly specific immune-based therapeutic strategies. Among these, chimeric antigen receptor (CAR) T cells have shown unparalleled therapeutic potential in treating refractory hematological malignancies. In contrast, solid tumors pose a much greater challenge to CAR T cell therapy, which has yet to be overcome. As this novel therapeutic modality matures, increasing effort is being invested to determine the optimal structure and properties of CARs to facilitate the transition from empirical testing to the rational design of CAR T cells. In this review, we highlight how individual CAR domains contribute to the success and failure of this promising treatment modality and provide an insight into the most notable advances in the field of CAR T cell engineering.
Highlights
The ability of immune cells to detect and destroy cancer cells forms the basis of all modern immunotherapies, including cancer vaccines, checkpoint blockade, and adoptive cell transfer (ACT).These distinct approaches to immunotherapy have been extensively reviewed elsewhere [1,2,3].ACT relies on the ability to generate large numbers of tumor-specific T cells
Gomes da Silva and colleagues reported that high anti-CD19-chimeric antigen receptor (CAR) expression driven by the long terminal repeat (LTR) of the SFG γ-retroviral vector led to antigen-independent tonic 4-1BB signaling, which resulted in Fas-dependent apoptosis of CAR T cells [34]
Constructs become more complex, a thorough understanding of the impact of distinct domains would likely improve the rational design of CAR T cells to suit the specific needs of individual patients
Summary
The ability of immune cells to detect and destroy cancer cells forms the basis of all modern immunotherapies, including cancer vaccines, checkpoint blockade, and adoptive cell transfer (ACT). A CAR usually consists of an antibody-derived single-chain variable displayed poor anti-tumor efficacy in patients, owing to the limited expansion and persistence of fragment (scFv), which is linked via a spacer and transmembrane domain to intracellular signaling transferredmolecules, Tcells [11,12,13]. Antigen syndrome [19,20], cytokine release syndrome [19,21,22], neurotoxicity [23,24] and on-target off-tumor the consequent tumor escape limit the long-term success of CAR T cell therapy in a significant fraction toxicity [25,26,27,28] have emerged, some with devastating consequences.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
