ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinoma
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...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Dental Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fdmed.2023.1116402/full |
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| author | Saffron E. Summers Saffron E. Summers Vehid Salih Andrew D. Foey |
| author_facet | Saffron E. Summers Saffron E. Summers Vehid Salih Andrew D. Foey |
| author_sort | Saffron E. Summers |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9fdb0c56d3004fe3a67240ab1f5f5172 |
| institution | Kabale University |
| issn | 2673-4915 |
| language | English |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Dental Medicine |
| spelling | doaj-art-9fdb0c56d3004fe3a67240ab1f5f51722025-02-11T10:29:09ZengFrontiers Media S.A.Frontiers in Dental Medicine2673-49152023-03-01410.3389/fdmed.2023.11164021116402ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinomaSaffron E. Summers0Saffron E. Summers1Vehid Salih2Andrew D. Foey3School of Biomedical Sciences, Faculty of Health, University of Plymouth, Plymouth, United KingdomSchool of Dentistry, Faculty of Health, University of Plymouth, Plymouth, United KingdomSchool of Dentistry, Faculty of Health, University of Plymouth, Plymouth, United KingdomSchool of Biomedical Sciences, Faculty of Health, University of Plymouth, Plymouth, United KingdomChimeric 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.https://www.frontiersin.org/articles/10.3389/fdmed.2023.1116402/fullCAR-TsPD-L1TAMsErbBMUC1OSCC |
| spellingShingle | Saffron E. Summers Saffron E. Summers Vehid Salih Andrew D. Foey ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinoma Frontiers in Dental Medicine CAR-Ts PD-L1 TAMs ErbB MUC1 OSCC |
| title | ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinoma |
| title_full | ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinoma |
| title_fullStr | ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinoma |
| title_full_unstemmed | ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinoma |
| title_short | ErbB- and MUC1-targeted CAR-T cell immunotherapy of oral squamous cell carcinoma |
| title_sort | erbb and muc1 targeted car t cell immunotherapy of oral squamous cell carcinoma |
| topic | CAR-Ts PD-L1 TAMs ErbB MUC1 OSCC |
| url | https://www.frontiersin.org/articles/10.3389/fdmed.2023.1116402/full |
| work_keys_str_mv | AT saffronesummers erbbandmuc1targetedcartcellimmunotherapyoforalsquamouscellcarcinoma AT saffronesummers erbbandmuc1targetedcartcellimmunotherapyoforalsquamouscellcarcinoma AT vehidsalih erbbandmuc1targetedcartcellimmunotherapyoforalsquamouscellcarcinoma AT andrewdfoey erbbandmuc1targetedcartcellimmunotherapyoforalsquamouscellcarcinoma |