Significantly increased anti‐tumor activity of carcinoembryonic antigen‐specific chimeric antigen receptor T cells in combination with recombinant human IL‐12
Abstract Background aims Chimeric antigen receptor T cells (CAR‐T cells) have been successfully used in treatments of hematological tumors, however, their anti‐tumor activity in solid tumor treatments was limited. As IL‐12 increases T‐cell immune functions, we designed carcinoembryonic antigen (CEA)...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-08-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2361 |
| _version_ | 1827968110828716032 |
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| author | Xiaowei Chi Peiwei Yang Erhao Zhang Jieyi Gu Hui Xu Mengwei Li Xinmei Gao Xin Li Yinan Zhang Hanmei Xu Jialiang Hu |
| author_facet | Xiaowei Chi Peiwei Yang Erhao Zhang Jieyi Gu Hui Xu Mengwei Li Xinmei Gao Xin Li Yinan Zhang Hanmei Xu Jialiang Hu |
| author_sort | Xiaowei Chi |
| collection | DOAJ |
| description | Abstract Background aims Chimeric antigen receptor T cells (CAR‐T cells) have been successfully used in treatments of hematological tumors, however, their anti‐tumor activity in solid tumor treatments was limited. As IL‐12 increases T‐cell immune functions, we designed carcinoembryonic antigen (CEA) specific CAR‐T (CEA‐CAR‐T) cells and, for the first time, used them in combination with recombinant human IL‐12 (rhIL‐12) to treat several types of solid tumors. Methods In vitro anti‐tumor activity of CEA‐CAR‐T cells in combination with rhIL‐12 was confirmed by evaluation of CEA‐CAR‐T cell activation, proliferation, and cytotoxicity after co‐incubation with CEA‐positive or CEA‐negative human tumor cells. In vivo anti‐tumor activity of CEA‐CAR‐T cells in combination with rhIL‐12 was confirmed in a xenograft model in nude mice for treatments of several types of solid tumors. Results In vitro experiments confirmed that rhIL‐12 significantly increased the activation, proliferation, and cytotoxicity of CEA‐CAR‐T cells. Similarly, in vivo experiments found that CEA‐CAR‐T cells in combination with rhIL‐12 had significantly enhanced anti‐tumor activity than CEA‐CAR‐T cells in growth inhibition of newly colonized colorectal cancer cell HT‐29, pancreatic cancer cell AsPC‐1, and gastric cancer cell MGC803. Conclusions These works confirmed that simultaneous use of cytokines, for example, rhIL‐12, can increase the anti‐tumor activity of CAR‐T cells, especially for treatments of several types of solid tumors. |
| first_indexed | 2024-04-09T18:16:08Z |
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| id | doaj.art-d9a7a0f34b6e488d95cc70228e2571fe |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-09T18:16:08Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-d9a7a0f34b6e488d95cc70228e2571fe2023-04-13T04:36:19ZengWileyCancer Medicine2045-76342019-08-018104753476510.1002/cam4.2361Significantly increased anti‐tumor activity of carcinoembryonic antigen‐specific chimeric antigen receptor T cells in combination with recombinant human IL‐12Xiaowei Chi0Peiwei Yang1Erhao Zhang2Jieyi Gu3Hui Xu4Mengwei Li5Xinmei Gao6Xin Li7Yinan Zhang8Hanmei Xu9Jialiang Hu10The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaThe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province Nanjing P. R. ChinaAbstract Background aims Chimeric antigen receptor T cells (CAR‐T cells) have been successfully used in treatments of hematological tumors, however, their anti‐tumor activity in solid tumor treatments was limited. As IL‐12 increases T‐cell immune functions, we designed carcinoembryonic antigen (CEA) specific CAR‐T (CEA‐CAR‐T) cells and, for the first time, used them in combination with recombinant human IL‐12 (rhIL‐12) to treat several types of solid tumors. Methods In vitro anti‐tumor activity of CEA‐CAR‐T cells in combination with rhIL‐12 was confirmed by evaluation of CEA‐CAR‐T cell activation, proliferation, and cytotoxicity after co‐incubation with CEA‐positive or CEA‐negative human tumor cells. In vivo anti‐tumor activity of CEA‐CAR‐T cells in combination with rhIL‐12 was confirmed in a xenograft model in nude mice for treatments of several types of solid tumors. Results In vitro experiments confirmed that rhIL‐12 significantly increased the activation, proliferation, and cytotoxicity of CEA‐CAR‐T cells. Similarly, in vivo experiments found that CEA‐CAR‐T cells in combination with rhIL‐12 had significantly enhanced anti‐tumor activity than CEA‐CAR‐T cells in growth inhibition of newly colonized colorectal cancer cell HT‐29, pancreatic cancer cell AsPC‐1, and gastric cancer cell MGC803. Conclusions These works confirmed that simultaneous use of cytokines, for example, rhIL‐12, can increase the anti‐tumor activity of CAR‐T cells, especially for treatments of several types of solid tumors.https://doi.org/10.1002/cam4.2361carcinoembryonic antigenchimeric antigen receptor T cellcolorectal cancergastric cancerIL‐12pancreatic cancer |
| spellingShingle | Xiaowei Chi Peiwei Yang Erhao Zhang Jieyi Gu Hui Xu Mengwei Li Xinmei Gao Xin Li Yinan Zhang Hanmei Xu Jialiang Hu Significantly increased anti‐tumor activity of carcinoembryonic antigen‐specific chimeric antigen receptor T cells in combination with recombinant human IL‐12 Cancer Medicine carcinoembryonic antigen chimeric antigen receptor T cell colorectal cancer gastric cancer IL‐12 pancreatic cancer |
| title | Significantly increased anti‐tumor activity of carcinoembryonic antigen‐specific chimeric antigen receptor T cells in combination with recombinant human IL‐12 |
| title_full | Significantly increased anti‐tumor activity of carcinoembryonic antigen‐specific chimeric antigen receptor T cells in combination with recombinant human IL‐12 |
| title_fullStr | Significantly increased anti‐tumor activity of carcinoembryonic antigen‐specific chimeric antigen receptor T cells in combination with recombinant human IL‐12 |
| title_full_unstemmed | Significantly increased anti‐tumor activity of carcinoembryonic antigen‐specific chimeric antigen receptor T cells in combination with recombinant human IL‐12 |
| title_short | Significantly increased anti‐tumor activity of carcinoembryonic antigen‐specific chimeric antigen receptor T cells in combination with recombinant human IL‐12 |
| title_sort | significantly increased anti tumor activity of carcinoembryonic antigen specific chimeric antigen receptor t cells in combination with recombinant human il 12 |
| topic | carcinoembryonic antigen chimeric antigen receptor T cell colorectal cancer gastric cancer IL‐12 pancreatic cancer |
| url | https://doi.org/10.1002/cam4.2361 |
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