| Autor: |
Roselli E; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA., Frieling JS; Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA., Thorner K; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA., Ramello MC; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA., Lynch CC; Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA., Abate-Daga D; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. Daniel.AbateDaga@moffitt.org.; Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. Daniel.AbateDaga@moffitt.org.; Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. Daniel.AbateDaga@moffitt.org.; Department of Oncologic Sciences, Morsani School of Medicine, University of South Florida, Tampa, FL, 33612, USA. Daniel.AbateDaga@moffitt.org. |
| Abstrakt: |
The adoptive transfer of genetically engineered T cells expressing a chimeric antigen receptor (CAR) has shown remarkable results against B cell malignancies. This immunotherapeutic approach has advanced and expanded rapidly from preclinical models to the recent approval of CAR-T cells to treat lymphomas and leukemia by the Food and Drug Administration (FDA). Ongoing research efforts are focused on employing CAR-T cells as a therapy for other cancers, and enhancing their efficacy and safety by optimizing their design. Here we summarize modifications in the intracellular domain of the CAR that gave rise to first-, second-, third- and next-generation CAR-T cells, together with the impact that these different designs have on CAR-T cell biology and function. Further, we describe how the structure of the antigen-sensing ectodomain can be enhanced, leading to superior CAR-T cell signaling and/or function. Finally we discuss how tissue-specific factors may impact the clinical efficacy of CAR-T cells for bone and the central nervous system, as examples of specific indications that may require further CAR signaling optimization to perform in such inhospitable microenvironments. |
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