Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells
Abstract The use of chimeric antigen receptor (CAR)-T cells has enhanced the range of available therapeutic modalities in the context of cancer treatment. CAR-T cells have demonstrated considerable efficacy in the targeted eradication of blood cancer cells, thereby stimulating substantial interest i...
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| Format: | Article |
| Language: | English |
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03817-z |
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| author | Marat Khaliulin Aygul Valiullina Alexey Petukhov Youyong Yuan Sheila Spada Emil Bulatov |
| author_facet | Marat Khaliulin Aygul Valiullina Alexey Petukhov Youyong Yuan Sheila Spada Emil Bulatov |
| author_sort | Marat Khaliulin |
| collection | DOAJ |
| description | Abstract The use of chimeric antigen receptor (CAR)-T cells has enhanced the range of available therapeutic modalities in the context of cancer treatment. CAR-T cells have demonstrated considerable efficacy in the targeted eradication of blood cancer cells, thereby stimulating substantial interest in the advancement of such therapeutic approaches. However, the efficacy of CAR-T cells against solid tumor cells has been limited due to the presence of various obstacles. Solid tumors exhibit antigenic diversity and an immunosuppressive microenvironment, which presents a challenge for immune cells attempting to penetrate the tumor. CAR-T cells also demonstrate decreased proliferative activity and cytotoxicity. Furthermore, concerns exist regarding tumor antigen loss and therapy-associated toxicity. Currently, scientists are working to enhance the structure of the CAR and improve the survival and efficiency of CAR-T cells in recognizing tumor antigens in solid tumors. Chemotherapy drugs are frequently employed in the treatment of malignant neoplasms and can also be used prior to cell therapy to enhance CAR-T cell engraftment. Recent studies have demonstrated that chemotherapy drugs can mitigate the suppressive impact of TME, eliminate the physical barrier by destroying the tumor stroma, and facilitate greater penetration of immune cells and CAR-T cells into the tumor. This, in turn, increases their survival, persistence, and cytotoxicity, as well as affects the metabolism of immune cells inside the tumor. However, the effectiveness of the combined approach against solid tumors depends on several factors, including the type of tumor, dosage, population of CAR-T cells, and individual characteristics of the body. This review examines the principal obstacles to the utilization of CAR-T cells against solid tumors, proposes solutions to these issues, and assesses the potential advantages of a combined approach to radiation exposure, which has the potential to enhance the sensitivity of the tumor to other agents. |
| format | Article |
| id | doaj-art-cb6cd5801ac34e3b846c3df3d635fc37 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-cb6cd5801ac34e3b846c3df3d635fc372025-02-02T12:26:54ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111210.1007/s00262-024-03817-zBreaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cellsMarat Khaliulin0Aygul Valiullina1Alexey Petukhov2Youyong Yuan3Sheila Spada4Emil Bulatov5Institute of Fundamental Medicine and Biology, Kazan Federal UniversityInstitute of Fundamental Medicine and Biology, Kazan Federal UniversityNazarbaev UniversitySchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of TechnologyTumor Immunology and Immunotherapy Unit, IRCCS-Regina Elena National Cancer InstituteInstitute of Fundamental Medicine and Biology, Kazan Federal UniversityAbstract The use of chimeric antigen receptor (CAR)-T cells has enhanced the range of available therapeutic modalities in the context of cancer treatment. CAR-T cells have demonstrated considerable efficacy in the targeted eradication of blood cancer cells, thereby stimulating substantial interest in the advancement of such therapeutic approaches. However, the efficacy of CAR-T cells against solid tumor cells has been limited due to the presence of various obstacles. Solid tumors exhibit antigenic diversity and an immunosuppressive microenvironment, which presents a challenge for immune cells attempting to penetrate the tumor. CAR-T cells also demonstrate decreased proliferative activity and cytotoxicity. Furthermore, concerns exist regarding tumor antigen loss and therapy-associated toxicity. Currently, scientists are working to enhance the structure of the CAR and improve the survival and efficiency of CAR-T cells in recognizing tumor antigens in solid tumors. Chemotherapy drugs are frequently employed in the treatment of malignant neoplasms and can also be used prior to cell therapy to enhance CAR-T cell engraftment. Recent studies have demonstrated that chemotherapy drugs can mitigate the suppressive impact of TME, eliminate the physical barrier by destroying the tumor stroma, and facilitate greater penetration of immune cells and CAR-T cells into the tumor. This, in turn, increases their survival, persistence, and cytotoxicity, as well as affects the metabolism of immune cells inside the tumor. However, the effectiveness of the combined approach against solid tumors depends on several factors, including the type of tumor, dosage, population of CAR-T cells, and individual characteristics of the body. This review examines the principal obstacles to the utilization of CAR-T cells against solid tumors, proposes solutions to these issues, and assesses the potential advantages of a combined approach to radiation exposure, which has the potential to enhance the sensitivity of the tumor to other agents.https://doi.org/10.1007/s00262-024-03817-zCAR-T cell therapyChemotherapyRadiation therapyChimeric antigen receptorSolid tumor |
| spellingShingle | Marat Khaliulin Aygul Valiullina Alexey Petukhov Youyong Yuan Sheila Spada Emil Bulatov Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells Cancer Immunology, Immunotherapy CAR-T cell therapy Chemotherapy Radiation therapy Chimeric antigen receptor Solid tumor |
| title | Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells |
| title_full | Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells |
| title_fullStr | Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells |
| title_full_unstemmed | Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells |
| title_short | Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells |
| title_sort | breaking the shield of solid tumors a combined approach for enhanced efficacy of car t cells |
| topic | CAR-T cell therapy Chemotherapy Radiation therapy Chimeric antigen receptor Solid tumor |
| url | https://doi.org/10.1007/s00262-024-03817-z |
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