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Review
. 2017 Dec;8(12):896-925.
doi: 10.1007/s13238-017-0400-z. Epub 2017 May 2.

Current status and perspectives of chimeric antigen receptor modified T cells for cancer treatment

Zhenguang Wang  1 , Yelei Guo  1 , Weidong Han  2
Affiliations
Review

Current status and perspectives of chimeric antigen receptor modified T cells for cancer treatment

Zhenguang Wang et al. Protein Cell. 2017 Dec.

Abstract

Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL)). Given this success, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.

Keywords: CAR-T; adoptive cell therapy; cancer treatment; chimeric antigen receptor; engineered T cells.

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Figures

Figure 1
Figure 1
Evolution of CAR
Figure 2
Figure 2
Anatomy of a second-generation CAR
Figure 3
Figure 3
Common second-generation CARs. Abbreviations: B-ALL, B cell acute lymphoblastic leukemia; BCM, Baylor College of Medicine; B-NHL, B cell non -Hodgkin’s lymphoma; CCA, cholangiocarcinoma; CLL, chronic lymphocytic leukemia; CMPC, castrate metastatic prostate cancer; EGFR, epidermal growth factor receptor; EGFRvIII, variant III of the epidermal growth factor receptor; FHCRC, Fred Hutchinson Cancer Research Center; GBM, glioblastoma multiforme; HER2, human epidermal growth factor receptor-2; HL, Hodgkin’s lymphoma; MM, multiple myeloma; MPD, malignant pleural disease; MPM, malignant pleural mesothelioma; MSKCC, Memorial Sloan Kettering Cancer Center; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; PC, pancreatic cancer; PDAC, pancreatic ductal adenocarcinoma; PLAGH, Chinese PLA General Hospital; PSMA, prostate-specific membrane antigen; scFv, single chain variable fragment; Upenn, University of Pennsylvania
See this image and copyright information in PMC

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