Chimeric Antigen Receptor (CAR) T Cell for Pediatric Solid Tumors: The Next Frontier in Cancer Treatment

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Combiningthe advancements in genetic engineering technologies and the principle knowledge of cancer immunology, chimeric antigen receptor (CAR) T cell therapy has emerged as a promising therapeutic modality for cancers. The function of CARs is to redirect the immune response to attack cancer cells in a specific manner. Up to date, multiple CAR configurations have been designed to ensure safety and to enhance in vivo persistence and therapeutic potency. A number of clinical trials of CAR T therapy for pediatric solid tumors are underway, mainly focusing on neuroblastoma patients. Although CAR T therapy has been approved by the US Food and Drug Administration (FDA) for hematological malignancies, disappointing response rates have been reported in solid cancers due to several hindrances. Proper target antigen selection, inefficient T cell trafficking, and the immunosuppressive nature of the tumor microenvironment (TME) are the main factors limiting CAR T function. In order for CAR T therapy to become successful in this matter, these challenges must be addressed. The future of CAR T therapy is moving toward the development of the "off-the-shelf" universal CAR T product in the hope of providing cancer treatment to a large population. This chapter reviews the principles of CAR design, current clinical trials, limitations, and future prospects of CAR T cells for pediatric solid tumors.