An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment
Adoptive cellular therapy with chimeric antigen receptor (CAR) T cells has emerged as a potential novel treatment for various cancers. In this study, we have generated CAR T cells targeting mucin-1 (MUC1), which is an aberrantly glycosylated antigen overexpressed on breast cancer cells. Two differen...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/2449373 |
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| author | Nattarika Khuisangeam Sirirut Jewmoung Rattapoom Thaiwong Suparat Tudsamran Nattiya Hirankarn Koramit Suppipat Supannikar Tawinwung |
| author_facet | Nattarika Khuisangeam Sirirut Jewmoung Rattapoom Thaiwong Suparat Tudsamran Nattiya Hirankarn Koramit Suppipat Supannikar Tawinwung |
| author_sort | Nattarika Khuisangeam |
| collection | DOAJ |
| description | Adoptive cellular therapy with chimeric antigen receptor (CAR) T cells has emerged as a potential novel treatment for various cancers. In this study, we have generated CAR T cells targeting mucin-1 (MUC1), which is an aberrantly glycosylated antigen overexpressed on breast cancer cells. Two different signaling domains, including CD28 and 41BB, were incorporated and directly compared the superiority of different costimulatory signals. Two different CAR MUC1 constructs were transduced into primary T cells and evaluated their characteristics and antitumor activities against MUC1+ cancer cells. CAR MUC1 T cells showed high transduction efficiency and antigen specificity toward MUC1+ cancer cell lines and primary breast cancer cells. When coculturing with target cells, the transduced cells exhibited potent antitumor activity in vitro and secrete proinflammatory cytokines. Upon antigen stimulation, incorporation of the 41BB signaling domain was able to improve T cell proliferation and reduce surface PD1 expression and the upregulation of suppressive cytokines, when compared with CAR MUC1 containing the CD28 domain. Our findings show that CAR T cell targeting MUC1 can be effective against MUC1+ breast cancer cell and support the further development of CAR MUC1 T cells containing 41BB signaling in preclinical and clinical studies of breast cancer treatment. |
| format | Article |
| id | doaj-art-0d2c9b4e97b544c382dc9e4c731a3c01 |
| institution | OA Journals |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-0d2c9b4e97b544c382dc9e4c731a3c012025-08-20T02:03:04ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/2449373An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer TreatmentNattarika Khuisangeam0Sirirut Jewmoung1Rattapoom Thaiwong2Suparat Tudsamran3Nattiya Hirankarn4Koramit Suppipat5Supannikar Tawinwung6Department of MicrobiologyChulalongkorn Comprehensive Cancer CenterChulalongkorn Comprehensive Cancer CenterChulalongkorn Comprehensive Cancer CenterDepartment of MicrobiologyChulalongkorn Comprehensive Cancer CenterCellular Immunotherapy Research UnitAdoptive cellular therapy with chimeric antigen receptor (CAR) T cells has emerged as a potential novel treatment for various cancers. In this study, we have generated CAR T cells targeting mucin-1 (MUC1), which is an aberrantly glycosylated antigen overexpressed on breast cancer cells. Two different signaling domains, including CD28 and 41BB, were incorporated and directly compared the superiority of different costimulatory signals. Two different CAR MUC1 constructs were transduced into primary T cells and evaluated their characteristics and antitumor activities against MUC1+ cancer cells. CAR MUC1 T cells showed high transduction efficiency and antigen specificity toward MUC1+ cancer cell lines and primary breast cancer cells. When coculturing with target cells, the transduced cells exhibited potent antitumor activity in vitro and secrete proinflammatory cytokines. Upon antigen stimulation, incorporation of the 41BB signaling domain was able to improve T cell proliferation and reduce surface PD1 expression and the upregulation of suppressive cytokines, when compared with CAR MUC1 containing the CD28 domain. Our findings show that CAR T cell targeting MUC1 can be effective against MUC1+ breast cancer cell and support the further development of CAR MUC1 T cells containing 41BB signaling in preclinical and clinical studies of breast cancer treatment.http://dx.doi.org/10.1155/2022/2449373 |
| spellingShingle | Nattarika Khuisangeam Sirirut Jewmoung Rattapoom Thaiwong Suparat Tudsamran Nattiya Hirankarn Koramit Suppipat Supannikar Tawinwung An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment Journal of Immunology Research |
| title | An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment |
| title_full | An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment |
| title_fullStr | An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment |
| title_full_unstemmed | An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment |
| title_short | An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment |
| title_sort | in vitro comparison of costimulatory domains in chimeric antigen receptor t cell for breast cancer treatment |
| url | http://dx.doi.org/10.1155/2022/2449373 |
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