Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspect
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REVIEW
Chimeric antigen receptor (CAR)‑T‑cell therapy in non‑small‑cell lung cancer (NSCLC): current status and future perspectives Jingjing Qu1,4 · Quanhui Mei3 · Lijun Chen2,5 · Jianying Zhou1 Received: 20 March 2020 / Accepted: 20 September 2020 © The Author(s) 2020
Abstract There has been a rapid progress in developing genetically engineered T cells in recent years both in basic and clinical cancer studies. Chimeric antigen receptor (CAR)-T cells exert an immune response against various cancers, including the nonsmall-cell lung cancer (NSCLC). As novel agents of immunotherapy, CAR-T cells show great promise for NSCLC. However, targeting specific antigens in NSCLC with engineered CAR-T cells is complicated because of a lack of tumor-specific antigens, the immunosuppressive tumor microenvironment, low levels of infiltration of CAR-T cells into tumor tissue, and tumor antigen escape. Meanwhile, the clinical application of CAR-T cells remains limited due to the cases of on-target/offtumor and neurological toxicity, as well as cytokine release syndrome. Hence, optimal CAR-T-cell design against NSCLC is urgently needed. In this review, we describe the basic structure and generation of CAR-T cells and summarize the common tumor-associated antigens targeted in clinical trials on CAR-T-cell therapy for NSCLC, as well as point out current challenges and novel strategies. Although many obstacles remain, the new/next generation of CARs show much promise. Taken together, research on CAR-T cells for the treatment of NSCLC is underway and has yielded promising preliminary results both in basic and pre-clinical medicine. More pre-clinical experiments and clinical trials are, therefore, warranted. Keywords CAR-T-cell therapy · Non-small-cell lung cancer · Immunotherapy · Future perspective · Tumor microenvironment Abbreviations CAR Chimeric antigen receptor CEA Carcinoembryonic antigen CRS Cytokine release syndrome CXCR C-X-C chemokine receptor EGFR Epidermal growth factor receptor Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02735-0) contains supplementary material, which is available to authorized users.
GITR Glucocorticoid-induced TNF receptorrelated protein HER1 Human epidermal receptor 1 HER2 Human epidermal growth factor receptor 2 HLA Human leukocyte antigen iCasp9M28z Inducible caspase 9-M28z ICOS Inducible costimulator IFN Interferon IL Interleukin
* Lijun Chen [email protected] * Jianying Zhou [email protected] 1
2
College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, People’s Republic of China 3
Department of Respiratory Disease, Thoracic Disease Centre, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, People’s Republic of China
Department of Intensive Care Unit, The First People’s Hospital of Changde City, Changde, Hunan 415003, People’s Republic of China
4
State Key Laboratory for Diagnosis and Treatment of Infectiou
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