ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinoma

免疫疗法 嵌合抗原受体 癌症研究 医学 头颈部鳞状细胞癌 癌症 靶向治疗 T细胞 肿瘤微环境 抗原 免疫系统 免疫学 肿瘤科 头颈部癌 内科学
作者
Saffron E. Summers,Vehid Salih,Andrew Foey
出处
期刊:Frontiers in dental medicine [Frontiers Media]
卷期号:4 被引量:1
标识
DOI:10.3389/fdmed.2023.1116402
摘要

Chimeric antigen receptor T (CAR-T) cell therapy has shown great success in treating B cell malignancies; however, there are many challenges that limit their therapeutic efficacy in solid tumours. Immunotherapy of head and neck squamous cell carcinoma (HNSCC), and, in particular, oral squamous cell carcinoma (OSCC), presents a unique set of challenges including lack of consistently expressed tumour associated antigens (TAAs) and the immunosuppressive tumour microenvironment (TME). Currently, there are few clinical trials investigating the use of CAR-T cells in HNSCC/OSCC; however, results from trials investigating similar solid tumours, such as breast cancer, can be adopted to help evaluate the use of CAR-T in this cancer. In this review, the process of CAR-T cell engineering and different generations of these cells will be summarised, highlighting their potential use in treating HNSCC through targeting ErbB and MUC1; TAAs highly expressed by this solid tumour. Potential strategies including combination therapy, utilising both TAA-targeting CAR-Ts and immune checkpoint inhibitors, such as PD-L1, have been discussed, in an attempt to develop synergistic anti-tumour responses. In addition to this, the use of dual-targeting CAR-T cells, synthetic NOTCH (synNOTCH) receptors and alternative non-tumour targets of the TME have been reviewed. Such combination therapies have been shown to help limit solid tumour progression and enhance both the safety and efficacy of CAR-T cell immunotherapy, which may be adopted for the treatment and management of OSCC.
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