Tumor buster - where will the CAR-T cell therapy 'missile' go?

Chunrun Qu; Hao Zhang; Hui Cao; Lanhua Tang; Haoyang Mo; Fangkun Liu; Liyang Zhang; Zhenjie Yi; Lifu Long; Luzhe Yan; Zeyu Wang; Nan Zhang; Peng Luo; Jian Zhang; Zaoqu Liu; Weijie Ye; Zhixiong Liu; Quan Cheng

doi:10.1186/s12943-022-01669-8

Tumor buster - where will the CAR-T cell therapy 'missile' go?

Mol Cancer. 2022 Oct 19;21(1):201. doi: 10.1186/s12943-022-01669-8.

Authors

Chunrun Qu^#^{1

2

3}, Hao Zhang^#^{1

3

4}, Hui Cao^{5

6}, Lanhua Tang⁷, Haoyang Mo^{1

2

3}, Fangkun Liu^{1

3}, Liyang Zhang^{1

3}, Zhenjie Yi^{1

2

3}, Lifu Long^{1

2

3}, Luzhe Yan², Zeyu Wang^{1

3}, Nan Zhang^{1

8}, Peng Luo⁹, Jian Zhang⁹, Zaoqu Liu¹⁰, Weijie Ye¹¹, Zhixiong Liu^{12

13}, Quan Cheng^{14

15}

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² XiangYa School of Medicine, Central South University, Changsha, Hunan, China.
³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
⁵ Department of Psychiatry, The Second People's Hospital of Hunan Province, The Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
⁶ The School of Clinical Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.
⁷ Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁸ One-third Lab, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
⁹ Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
¹⁰ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou, Zhengzhou, Henan, China.
¹¹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
¹² Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].
¹³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].
¹⁴ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].
¹⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].

^# Contributed equally.

Abstract

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies' clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

Keywords: CAR-T cell; Cancer; Immunotherapy; Personalized treatment; Target.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Neoplasm / genetics
Cell- and Tissue-Based Therapy
Humans
Immunotherapy, Adoptive / methods
Neoplasms* / genetics
Receptors, Chimeric Antigen* / genetics
Tumor Microenvironment

Substances

Receptors, Chimeric Antigen
Antigens, Neoplasm