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

• Published in: Molecular cancer 2022-10, Vol.21 (1), p.201-53, Article 201
• Main Authors: Qu, Chunrun, Zhang, Hao, Cao, Hui, Tang, Lanhua, Mo, Haoyang, Liu, Fangkun, Zhang, Liyang, Yi, Zhenjie, Long, Lifu, Yan, Luzhe, Wang, Zeyu, Zhang, Nan, Luo, Peng, Zhang, Jian, Liu, Zaoqu, Ye, Weijie, Liu, Zhixiong, Cheng, Quan
• Format: Article
• Language: English
• Subjects: Antigen (tumor-associated); Antigens; Antigens, Neoplasm - genetics; Apoptosis; Cancer; Cancer immunotherapy; Cancer therapies; CAR-T cell; Care and treatment; Cell therapy; Cell- and Tissue-Based Therapy; Chemotherapy; Chimeric antigen receptors; Clinical trials; Design; Disease; FDA approval; Genetic aspects; Genetically modified organisms; Genome editing; Health aspects; Hematological diseases; Humans; Immunotherapy; Immunotherapy, Adoptive - methods; Lymphocytes; Lymphocytes T; Lymphoma; Medical prognosis; Medical research; Neoplasms - genetics; Neurotoxicity; Oncology, Experimental; Patients; Personalized treatment; Prognosis; Receptors, Chimeric Antigen - genetics; Review; Solid tumors; T cell receptors; T cells; Target; Therapeutic targets; Toxicity; Tumor Microenvironment; Tumors
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-022-01669-8

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.