Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer
An in vitro culture period of at least 2 weeks is required to produce sufficient natural killer (NK) cells for immunotherapy, which are the key effectors in hematological malignancy treatment. Mitochondrial damage and fragmentation reduce the NK cell immune surveillance capacity. Thus, we hypothesiz...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/12/3225 |
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| author | Seong-Hoon Kim Mi-Jin Kim Mina Lim Jihye Kim Hyunmin Kim Chang-Koo Yun Yun-Joo Yoo Youngjun Lee Kyunghoon Min Yong-Soo Choi |
| author_facet | Seong-Hoon Kim Mi-Jin Kim Mina Lim Jihye Kim Hyunmin Kim Chang-Koo Yun Yun-Joo Yoo Youngjun Lee Kyunghoon Min Yong-Soo Choi |
| author_sort | Seong-Hoon Kim |
| collection | DOAJ |
| description | An in vitro culture period of at least 2 weeks is required to produce sufficient natural killer (NK) cells for immunotherapy, which are the key effectors in hematological malignancy treatment. Mitochondrial damage and fragmentation reduce the NK cell immune surveillance capacity. Thus, we hypothesized that the transfer of healthy mitochondria to NK cells could enhance their anticancer effects. Allogeneic healthy mitochondria isolated from WRL-68 cells were transferred to NK cells. We evaluated NK cells’ proliferative capacity, cell cycle, and cytotoxic capacity against various cancer cell types by analyzing specific lysis and the cytotoxic granules released. The relationship between the transferred allogenic mitochondrial residues and NK cell function was determined. After mitochondrial transfer, the NK cell proliferation rate was 1.2-fold higher than that of control cells. The mitochondria-treated NK cells secreted a 2.7-, 4.1-, and 5-fold higher amount of granzyme B, perforin, and IFN-γ, respectively, when co-cultured with K562 cells. The specific lysis of various solid cancer cells increased 1.3–1.6-fold. However, once allogeneic mitochondria were eliminated, the NK cell activity returned to the pre-mitochondrial transfer level. Mitochondria-enriched NK cells have the potential to be used as a novel solid cancer treatment agent, without the need for in vitro cytokine-induced culture. |
| first_indexed | 2024-03-09T03:23:16Z |
| format | Article |
| id | doaj.art-1cc23e4c836f47bfa9114c9b440cb7ce |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T03:23:16Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1cc23e4c836f47bfa9114c9b440cb7ce2023-12-03T15:05:36ZengMDPI AGCancers2072-66942023-06-011512322510.3390/cancers15123225Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial TransferSeong-Hoon Kim0Mi-Jin Kim1Mina Lim2Jihye Kim3Hyunmin Kim4Chang-Koo Yun5Yun-Joo Yoo6Youngjun Lee7Kyunghoon Min8Yong-Soo Choi9Department of Biotechnology, CHA University, Seongnam 13488, Republic of KoreaDepartment of Biotechnology, CHA University, Seongnam 13488, Republic of KoreaDepartment of Biotechnology, CHA University, Seongnam 13488, Republic of KoreaDepartment of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USADepartment of Biotechnology, CHA University, Seongnam 13488, Republic of KoreaDepartment of Biotechnology, CHA University, Seongnam 13488, Republic of KoreaResearch & Development Division, Humancellbio Co., Ltd., Suwon 16227, Republic of KoreaDepartment of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of KoreaDepartment of Biotechnology, CHA University, Seongnam 13488, Republic of KoreaAn in vitro culture period of at least 2 weeks is required to produce sufficient natural killer (NK) cells for immunotherapy, which are the key effectors in hematological malignancy treatment. Mitochondrial damage and fragmentation reduce the NK cell immune surveillance capacity. Thus, we hypothesized that the transfer of healthy mitochondria to NK cells could enhance their anticancer effects. Allogeneic healthy mitochondria isolated from WRL-68 cells were transferred to NK cells. We evaluated NK cells’ proliferative capacity, cell cycle, and cytotoxic capacity against various cancer cell types by analyzing specific lysis and the cytotoxic granules released. The relationship between the transferred allogenic mitochondrial residues and NK cell function was determined. After mitochondrial transfer, the NK cell proliferation rate was 1.2-fold higher than that of control cells. The mitochondria-treated NK cells secreted a 2.7-, 4.1-, and 5-fold higher amount of granzyme B, perforin, and IFN-γ, respectively, when co-cultured with K562 cells. The specific lysis of various solid cancer cells increased 1.3–1.6-fold. However, once allogeneic mitochondria were eliminated, the NK cell activity returned to the pre-mitochondrial transfer level. Mitochondria-enriched NK cells have the potential to be used as a novel solid cancer treatment agent, without the need for in vitro cytokine-induced culture.https://www.mdpi.com/2072-6694/15/12/3225natural killer cellsimmune cell therapymitochondriamitochondrial transferanticancer immunotherapy |
| spellingShingle | Seong-Hoon Kim Mi-Jin Kim Mina Lim Jihye Kim Hyunmin Kim Chang-Koo Yun Yun-Joo Yoo Youngjun Lee Kyunghoon Min Yong-Soo Choi Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer Cancers natural killer cells immune cell therapy mitochondria mitochondrial transfer anticancer immunotherapy |
| title | Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer |
| title_full | Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer |
| title_fullStr | Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer |
| title_full_unstemmed | Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer |
| title_short | Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer |
| title_sort | enhancement of the anticancer ability of natural killer cells through allogeneic mitochondrial transfer |
| topic | natural killer cells immune cell therapy mitochondria mitochondrial transfer anticancer immunotherapy |
| url | https://www.mdpi.com/2072-6694/15/12/3225 |
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