Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth
Vγ9Vδ2 T cells are immune effector cells capable of killing multiple myeloma (MM) cells and have been tested in clinical trials to treat MM patients. To enhance the MM cell killing function of Vγ9Vδ2 T cells, we introduced a BCMA-specific CAR into ex vivo expanded Vγ9Vδ2 T cells through electroporat...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202950/?tool=EBI |
| _version_ | 1811333907128254464 |
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| author | Xi Zhang Yu Yang Ng Zhicheng Du Zhendong Li Can Chen Lin Xiao Wee Joo Chng Shu Wang |
| author_facet | Xi Zhang Yu Yang Ng Zhicheng Du Zhendong Li Can Chen Lin Xiao Wee Joo Chng Shu Wang |
| author_sort | Xi Zhang |
| collection | DOAJ |
| description | Vγ9Vδ2 T cells are immune effector cells capable of killing multiple myeloma (MM) cells and have been tested in clinical trials to treat MM patients. To enhance the MM cell killing function of Vγ9Vδ2 T cells, we introduced a BCMA-specific CAR into ex vivo expanded Vγ9Vδ2 T cells through electroporation of the CAR-encoding mRNA. The modified Vγ9Vδ2 T cells displayed a high cytolytic activity against BCMA-expressing MM cell lines in vitro, while sparing BCMA-negative cells, including normal B cells and monocytes. Subsequently, we intravenously injected KMS-11 human MM cells to generate a xenograft mouse model. The treatment of the tumor-bearing mice with Zometa and anti-BCMA CAR- Vγ9Vδ2 T cells resulted in a significant reduction of tumor burden in the femur region, as well as the overall tumor burden. In association with the decrease in tumor burden, the survival of the MM cell-inoculated mice was markedly prolonged. Considering the potential of Vγ9Vδ2 T cells to be used as off-the-shelf products, the modification of these cells with a BCMA-specific CAR could be an attractive option for cancer immunotherapy against bone marrow cancer MM. |
| first_indexed | 2024-04-13T16:59:52Z |
| format | Article |
| id | doaj.art-c171c1a8b01c41bdbf89b4fb3d59170c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T16:59:52Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c171c1a8b01c41bdbf89b4fb3d59170c2022-12-22T02:38:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01176Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growthXi ZhangYu Yang NgZhicheng DuZhendong LiCan ChenLin XiaoWee Joo ChngShu WangVγ9Vδ2 T cells are immune effector cells capable of killing multiple myeloma (MM) cells and have been tested in clinical trials to treat MM patients. To enhance the MM cell killing function of Vγ9Vδ2 T cells, we introduced a BCMA-specific CAR into ex vivo expanded Vγ9Vδ2 T cells through electroporation of the CAR-encoding mRNA. The modified Vγ9Vδ2 T cells displayed a high cytolytic activity against BCMA-expressing MM cell lines in vitro, while sparing BCMA-negative cells, including normal B cells and monocytes. Subsequently, we intravenously injected KMS-11 human MM cells to generate a xenograft mouse model. The treatment of the tumor-bearing mice with Zometa and anti-BCMA CAR- Vγ9Vδ2 T cells resulted in a significant reduction of tumor burden in the femur region, as well as the overall tumor burden. In association with the decrease in tumor burden, the survival of the MM cell-inoculated mice was markedly prolonged. Considering the potential of Vγ9Vδ2 T cells to be used as off-the-shelf products, the modification of these cells with a BCMA-specific CAR could be an attractive option for cancer immunotherapy against bone marrow cancer MM.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202950/?tool=EBI |
| spellingShingle | Xi Zhang Yu Yang Ng Zhicheng Du Zhendong Li Can Chen Lin Xiao Wee Joo Chng Shu Wang Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth PLoS ONE |
| title | Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth |
| title_full | Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth |
| title_fullStr | Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth |
| title_full_unstemmed | Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth |
| title_short | Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth |
| title_sort | vγ9vδ2 t cells expressing a bcma specific chimeric antigen receptor inhibit multiple myeloma xenograft growth |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202950/?tool=EBI |
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