Third-Generation Anti-CD47-Specific CAR-T Cells Effectively Kill Cancer Cells and Reduce the Genes Expression in Lung Cancer Cell Metastasis
CD47 is a cell surface glycoprotein molecule, belonging to the immunoglobulin superfamily, binding to various proteins including integrins, thrombospondin-1, and signal regulatory protein α (SIRPα). CD47 is an important tumor antigen for the development and progression of various cancers. This study...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/5575260 |
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| _version_ | 1832561172013907968 |
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| author | Huyen Thi La Dao Bich Thi Tran Hai Manh Tran Linh Trong Nguyen |
| author_facet | Huyen Thi La Dao Bich Thi Tran Hai Manh Tran Linh Trong Nguyen |
| author_sort | Huyen Thi La |
| collection | DOAJ |
| description | CD47 is a cell surface glycoprotein molecule, belonging to the immunoglobulin superfamily, binding to various proteins including integrins, thrombospondin-1, and signal regulatory protein α (SIRPα). CD47 is an important tumor antigen for the development and progression of various cancers. This study designed the chimeric antigen receptor T-cell (CAR-T) to bind to the CD47 to inhibit the expression of CD47. We used the complementarity-determining regions (CDRs) of the B6H12 mouse antibody grafted onto the IgG1 framework to create the humanized single-chain variable fragment (scFv) with linker (G4S)x3. scFv was used to design the chimeric antigen receptor with the structure CD8signal-CD47scFv-CD8a hinge-CD4TM-CD28-41BB-CD3ζ, which was then transformed into T lymphocytes by the lentivirus to create third generation of CAR-T. Results revealed that the new CAR-T cells efficiently killed A549 cancer cells. CAR-T inhibited the expression of genes involved in metastasis and invasion of cells A549 including beta actin, calreticulin, and cyclooxygenase 2 at mRNA levels. |
| format | Article |
| id | doaj-art-b6a5cbce16a2457ba322ab35639052b0 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b6a5cbce16a2457ba322ab35639052b02025-02-03T01:25:48ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/55752605575260Third-Generation Anti-CD47-Specific CAR-T Cells Effectively Kill Cancer Cells and Reduce the Genes Expression in Lung Cancer Cell MetastasisHuyen Thi La0Dao Bich Thi Tran1Hai Manh Tran2Linh Trong Nguyen3Institute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, VietnamInstitute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, VietnamInstitute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, VietnamInstitute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, VietnamCD47 is a cell surface glycoprotein molecule, belonging to the immunoglobulin superfamily, binding to various proteins including integrins, thrombospondin-1, and signal regulatory protein α (SIRPα). CD47 is an important tumor antigen for the development and progression of various cancers. This study designed the chimeric antigen receptor T-cell (CAR-T) to bind to the CD47 to inhibit the expression of CD47. We used the complementarity-determining regions (CDRs) of the B6H12 mouse antibody grafted onto the IgG1 framework to create the humanized single-chain variable fragment (scFv) with linker (G4S)x3. scFv was used to design the chimeric antigen receptor with the structure CD8signal-CD47scFv-CD8a hinge-CD4TM-CD28-41BB-CD3ζ, which was then transformed into T lymphocytes by the lentivirus to create third generation of CAR-T. Results revealed that the new CAR-T cells efficiently killed A549 cancer cells. CAR-T inhibited the expression of genes involved in metastasis and invasion of cells A549 including beta actin, calreticulin, and cyclooxygenase 2 at mRNA levels.http://dx.doi.org/10.1155/2021/5575260 |
| spellingShingle | Huyen Thi La Dao Bich Thi Tran Hai Manh Tran Linh Trong Nguyen Third-Generation Anti-CD47-Specific CAR-T Cells Effectively Kill Cancer Cells and Reduce the Genes Expression in Lung Cancer Cell Metastasis Journal of Immunology Research |
| title | Third-Generation Anti-CD47-Specific CAR-T Cells Effectively Kill Cancer Cells and Reduce the Genes Expression in Lung Cancer Cell Metastasis |
| title_full | Third-Generation Anti-CD47-Specific CAR-T Cells Effectively Kill Cancer Cells and Reduce the Genes Expression in Lung Cancer Cell Metastasis |
| title_fullStr | Third-Generation Anti-CD47-Specific CAR-T Cells Effectively Kill Cancer Cells and Reduce the Genes Expression in Lung Cancer Cell Metastasis |
| title_full_unstemmed | Third-Generation Anti-CD47-Specific CAR-T Cells Effectively Kill Cancer Cells and Reduce the Genes Expression in Lung Cancer Cell Metastasis |
| title_short | Third-Generation Anti-CD47-Specific CAR-T Cells Effectively Kill Cancer Cells and Reduce the Genes Expression in Lung Cancer Cell Metastasis |
| title_sort | third generation anti cd47 specific car t cells effectively kill cancer cells and reduce the genes expression in lung cancer cell metastasis |
| url | http://dx.doi.org/10.1155/2021/5575260 |
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