Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells
Immunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic potent...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/14/2164 |
| _version_ | 1827624302861615104 |
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| author | Yunmi Ko Yeon Ho Jeong Jun Ah Lee |
| author_facet | Yunmi Ko Yeon Ho Jeong Jun Ah Lee |
| author_sort | Yunmi Ko |
| collection | DOAJ |
| description | Immunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic potential against OS cells. PBMCs from healthy donors were cultured for 10 days with CON medium (unstimulated control); EX media, CON with recombinant human interleukin-2 (rhIL-2) and zoledronate; and EX28 media, CON with rhIL-2, zoledronate, and CD3/CD28 activator. The expanded γδ T cells were isolated by magnetic cell separation or fluorescence-activated cell sorting, cultured with two OS cell lines (KHOS/NP and MG-63) at various cell ratios with or without doxorubicin or ifosfamide, and analyzed for cytotoxicity and cytokine secretion. The number of CD3<sup>+</sup>γδTCR<sup>+</sup>Vγ9<sup>+</sup> triple-positive γδ T cells and concentrations of IFN-γ and TNF-α were highest in the rhIL-2 (100 IU) and zoledronate (1 μM) supplemented culture conditions. The CD3/CD28 agonist did not show any additional effects on γδ T cell expansion. The expanded γδ T cells exhibited potent in vitro cytotoxicity against OS in a ratio- and time-dependent manner. The γδ T cells may enhance the effect of chemotherapeutic agents against OS and may be a new treatment strategy, including chemo-immunotherapy, for OS. |
| first_indexed | 2024-03-09T12:05:48Z |
| format | Article |
| id | doaj.art-81bc9fb0b571470cbcc720fe980c2b4a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T12:05:48Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-81bc9fb0b571470cbcc720fe980c2b4a2023-11-30T22:58:24ZengMDPI AGCells2073-44092022-07-011114216410.3390/cells11142164Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma CellsYunmi Ko0Yeon Ho Jeong1Jun Ah Lee2Center for Pediatric Cancer, Department of Pediatrics, National Cancer Center, Goyang 10408, KoreaDepartment of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, KoreaCenter for Pediatric Cancer, Department of Pediatrics, National Cancer Center, Goyang 10408, KoreaImmunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic potential against OS cells. PBMCs from healthy donors were cultured for 10 days with CON medium (unstimulated control); EX media, CON with recombinant human interleukin-2 (rhIL-2) and zoledronate; and EX28 media, CON with rhIL-2, zoledronate, and CD3/CD28 activator. The expanded γδ T cells were isolated by magnetic cell separation or fluorescence-activated cell sorting, cultured with two OS cell lines (KHOS/NP and MG-63) at various cell ratios with or without doxorubicin or ifosfamide, and analyzed for cytotoxicity and cytokine secretion. The number of CD3<sup>+</sup>γδTCR<sup>+</sup>Vγ9<sup>+</sup> triple-positive γδ T cells and concentrations of IFN-γ and TNF-α were highest in the rhIL-2 (100 IU) and zoledronate (1 μM) supplemented culture conditions. The CD3/CD28 agonist did not show any additional effects on γδ T cell expansion. The expanded γδ T cells exhibited potent in vitro cytotoxicity against OS in a ratio- and time-dependent manner. The γδ T cells may enhance the effect of chemotherapeutic agents against OS and may be a new treatment strategy, including chemo-immunotherapy, for OS.https://www.mdpi.com/2073-4409/11/14/2164chemo-immunotherapychemotherapeutic agentsimmunotherapymononuclear cellsosteosarcomaperipheral blood |
| spellingShingle | Yunmi Ko Yeon Ho Jeong Jun Ah Lee Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells Cells chemo-immunotherapy chemotherapeutic agents immunotherapy mononuclear cells osteosarcoma peripheral blood |
| title | Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells |
| title_full | Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells |
| title_fullStr | Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells |
| title_full_unstemmed | Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells |
| title_short | Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells |
| title_sort | therapeutic potential of ex vivo expanded γδ t cells against osteosarcoma cells |
| topic | chemo-immunotherapy chemotherapeutic agents immunotherapy mononuclear cells osteosarcoma peripheral blood |
| url | https://www.mdpi.com/2073-4409/11/14/2164 |
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