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Mol Cancer. 2018 Feb 15;17(1):32. doi: 10.1186/s12943-018-0814-0.

Engineering chimeric antigen receptor-T cells for cancer treatment.

Author information

1
Department of Hematology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
2
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, 94305-5117, USA.
3
Department of Neurosurgery, Xiangya Hospital, Central south University, Changsha, Hunan, 410008, China.
4
Lab of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Tianjin, China. kang97061@tmu.edu.cn.
5
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China. xiaoxingxiong@whu.edu.cn.

Abstract

Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion. Then we assess the functional challenges of CAR-T cell therapy, including cell trafficking and infiltration, targeted-recognition and killing of tumor cells, T-cell proliferation and persistence, immunosuppressive microenvironment and self-control regulation. Finally, we delineate tumor precision informatics and advancements in engineered CAR-T cells to counteract inherent challenges of the CAR-T cell therapy, either alone or in combination with traditional therapeutics, and highlight the therapeutic potential of this approach in future tumor precision treatment.

KEYWORDS:

Cancer immunotherapy; Chimeric antigen receptor (CAR) T cell therapy; Intratumor heterogeneity; T-cell exhaustion; Tumor ecosystem

PMID:
29448937
PMCID:
PMC5815249
DOI:
10.1186/s12943-018-0814-0
[Indexed for MEDLINE]
Free PMC Article

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