Looking forward for chimeric antigen receptor therapy
Chen, Kevin Hui
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Chimeric antigen receptors (CAR) are modular genetically modified receptors that consist of an extracellular antigen binding domain fused to intracellular T-cell signaling domains. CAR therapy broadly consists of engineering a patient’s own T-cells to express a CAR directed against a tumor cell surface antigen. This therapy has been extremely successful in treating B-cell neoplasms by targeting CD19 and is paradigm changing in developing personalized immunotherapy for oncology applications. Although impressive response rates are observed, the durability of therapeutic response remains a concern and relapse mechanisms frequently center around issues of antigen loss. In addition, heterogeneous disease and solid tumors present formidable barriers toward extending the applicability of CAR technology as a result of compounding issues of tumor microenvironment and cell trafficking. In this thesis we review the current thought on the state of CAR therapy and the challenges to therapeutic efficacy, therapeutic manufacture, and clinical safety in the context of each other with an overall emphasis on identifying the fundamental goal of making fit-for-purpose CARs for different diseases.
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