Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps

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• 作者：Gregory L. Beatty ; ^{gregory.beatty@uphs.upenn.edu" class="auth_mail" title="E-mail the corresponding author} ; Mark O'Hara
• 关键词：CAIX ; Carbonic anhydrase IX ; CAR ; Chimeric antigen receptor ; EGFR ; Epidermal growth factor receptor ; EGFRvIII ; Epidermal growth factor receptor variant III ; HSV-tk ; Herpes simplex thymidine kinase ; IDO ; Indoleamine 2 ; 3 dioxygenase ; IL ; Interleukin ; MHC ; Major histocompatibility ; synNotch ; Synthetic Notch receptor ; TCR ; T cell receptor
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：166
• 期：Complete
• 页码：30-39
• 全文大小：586 K

文摘

Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers to CAR T cell efficacy and mechanisms underlying these barriers, outline potential avenues for overcoming these therapeutic obstacles, and discuss the future of translating CAR T cells for the treatment of patients with solid malignancies.