Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma
Abstract Head and neck squamous cell carcinoma (HNSCC) remains among the most aggressive malignancies with limited treatment options, especially in recurrent and metastatic cases. Despite advances in surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitors, survival rates remain subopti...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Biomarker Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40364-025-00783-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850206603753553920 |
|---|---|
| author | Sahand Saeidpour Masouleh Kamyar Nasiri Ava Ostovar Ravari Mona Saligheh Rad Kiarash kiani Ali Sharifi Sultani Seyedeh Tabasom Nejati Mohsen Nabi Afjadi |
| author_facet | Sahand Saeidpour Masouleh Kamyar Nasiri Ava Ostovar Ravari Mona Saligheh Rad Kiarash kiani Ali Sharifi Sultani Seyedeh Tabasom Nejati Mohsen Nabi Afjadi |
| author_sort | Sahand Saeidpour Masouleh |
| collection | DOAJ |
| description | Abstract Head and neck squamous cell carcinoma (HNSCC) remains among the most aggressive malignancies with limited treatment options, especially in recurrent and metastatic cases. Despite advances in surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitors, survival rates remain suboptimal due to tumor heterogeneity, immune evasion, and treatment resistance. In recent years, Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized hematologic cancer treatment by genetically modifying T cells to target tumor-specific antigens like CD19, CD70, BCMA, EGFR, and HER2, leading to high remission rates. Its success is attributed to precise antigen recognition, sustained immune response, and long-term immunological memory, though challenges like cytokine release syndrome and antigen loss remain. Notably, its translation to solid tumors, including HNSCC, faces significant challenges, such as tumor microenvironment (TME)-induced immunosuppression, antigen heterogeneity, and limited CAR T-cell infiltration. To address these barriers, several tumor-associated antigens (TAAs), including EGFR, HER2 (ErbB2), B7-H3, CD44v6, CD70, CD98, and MUC1, have been identified as potential CAR T-cell targets in HNSCC. Moreover, innovative approaches, such as dual-targeted CAR T-cells, armored CARs, and CRISPR-engineered modifications, aim to enhance efficacy and overcome resistance. Notably, combination therapies integrating CAR T-cells with immune checkpoint inhibitors (e.g., PD-1/CTLA-4 blockade) and TGF-β-resistant CAR T designs are being explored to improve therapeutic outcomes. This review aimed to elucidate the current landscape of CAR T-cell therapy in HNSCC, by exploring its mechanisms, targeted antigens, challenges, emerging strategies, and future therapeutic potential. |
| format | Article |
| id | doaj-art-acf3b7bfb9b84382aaa2a641c3e815b6 |
| institution | OA Journals |
| issn | 2050-7771 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj-art-acf3b7bfb9b84382aaa2a641c3e815b62025-08-20T02:10:46ZengBMCBiomarker Research2050-77712025-05-0113112810.1186/s40364-025-00783-1Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinomaSahand Saeidpour Masouleh0Kamyar Nasiri1Ava Ostovar Ravari2Mona Saligheh Rad3Kiarash kiani4Ali Sharifi Sultani5Seyedeh Tabasom Nejati6Mohsen Nabi Afjadi7Department of Medical Biotechnologies, University of SienaFaculty of Dentistry, Islamic Azad University of Medical SciencesFaculty of Dentistry, Haybusak University of Medical SciencesFaculty of Dentistry, Islamic Azad University of Medical SciencesFaculty of Dentistry, Islamic Azad University of Medical SciencesFaculty of Dentistry, Iran University of Medical SciencesSchool of Dentistry, Hormozgan University of Medical SciencesDepartment of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares UniversityAbstract Head and neck squamous cell carcinoma (HNSCC) remains among the most aggressive malignancies with limited treatment options, especially in recurrent and metastatic cases. Despite advances in surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitors, survival rates remain suboptimal due to tumor heterogeneity, immune evasion, and treatment resistance. In recent years, Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized hematologic cancer treatment by genetically modifying T cells to target tumor-specific antigens like CD19, CD70, BCMA, EGFR, and HER2, leading to high remission rates. Its success is attributed to precise antigen recognition, sustained immune response, and long-term immunological memory, though challenges like cytokine release syndrome and antigen loss remain. Notably, its translation to solid tumors, including HNSCC, faces significant challenges, such as tumor microenvironment (TME)-induced immunosuppression, antigen heterogeneity, and limited CAR T-cell infiltration. To address these barriers, several tumor-associated antigens (TAAs), including EGFR, HER2 (ErbB2), B7-H3, CD44v6, CD70, CD98, and MUC1, have been identified as potential CAR T-cell targets in HNSCC. Moreover, innovative approaches, such as dual-targeted CAR T-cells, armored CARs, and CRISPR-engineered modifications, aim to enhance efficacy and overcome resistance. Notably, combination therapies integrating CAR T-cells with immune checkpoint inhibitors (e.g., PD-1/CTLA-4 blockade) and TGF-β-resistant CAR T designs are being explored to improve therapeutic outcomes. This review aimed to elucidate the current landscape of CAR T-cell therapy in HNSCC, by exploring its mechanisms, targeted antigens, challenges, emerging strategies, and future therapeutic potential.https://doi.org/10.1186/s40364-025-00783-1Head and neck squamous cell carcinomaChimeric antigen receptor T-cell therapyImmunotherapyCRISPR |
| spellingShingle | Sahand Saeidpour Masouleh Kamyar Nasiri Ava Ostovar Ravari Mona Saligheh Rad Kiarash kiani Ali Sharifi Sultani Seyedeh Tabasom Nejati Mohsen Nabi Afjadi Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma Biomarker Research Head and neck squamous cell carcinoma Chimeric antigen receptor T-cell therapy Immunotherapy CRISPR |
| title | Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma |
| title_full | Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma |
| title_fullStr | Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma |
| title_full_unstemmed | Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma |
| title_short | Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma |
| title_sort | advances and challenges in car t cell therapy for head and neck squamous cell carcinoma |
| topic | Head and neck squamous cell carcinoma Chimeric antigen receptor T-cell therapy Immunotherapy CRISPR |
| url | https://doi.org/10.1186/s40364-025-00783-1 |
| work_keys_str_mv | AT sahandsaeidpourmasouleh advancesandchallengesincartcelltherapyforheadandnecksquamouscellcarcinoma AT kamyarnasiri advancesandchallengesincartcelltherapyforheadandnecksquamouscellcarcinoma AT avaostovarravari advancesandchallengesincartcelltherapyforheadandnecksquamouscellcarcinoma AT monasalighehrad advancesandchallengesincartcelltherapyforheadandnecksquamouscellcarcinoma AT kiarashkiani advancesandchallengesincartcelltherapyforheadandnecksquamouscellcarcinoma AT alisharifisultani advancesandchallengesincartcelltherapyforheadandnecksquamouscellcarcinoma AT seyedehtabasomnejati advancesandchallengesincartcelltherapyforheadandnecksquamouscellcarcinoma AT mohsennabiafjadi advancesandchallengesincartcelltherapyforheadandnecksquamouscellcarcinoma |