Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells
Hematopoietic stem cells (HSCs) yield both the myeloid and lymphoid lineages of blood cells and can be reprogrammed into tumor antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) to prevent tumor growth. However, the optimal approach for differentiating tumor Ag-specific CTLs from HSCs, such a...
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MDPI AG
2018-07-01
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| Series: | Vaccines |
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| Online Access: | http://www.mdpi.com/2076-393X/6/3/40 |
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| author | Xiaofang Xiong Jugal Kishor Das Jianyong Song Bing Ni Xingcong Ren Jin-Ming Yang Jianxun Song |
| author_facet | Xiaofang Xiong Jugal Kishor Das Jianyong Song Bing Ni Xingcong Ren Jin-Ming Yang Jianxun Song |
| author_sort | Xiaofang Xiong |
| collection | DOAJ |
| description | Hematopoietic stem cells (HSCs) yield both the myeloid and lymphoid lineages of blood cells and can be reprogrammed into tumor antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) to prevent tumor growth. However, the optimal approach for differentiating tumor Ag-specific CTLs from HSCs, such as HSC-CTLs, remains elusive. In the current study, we showed that a combination of genetic modification of HSCs and in vivo T cell development facilitates the generation of Ag-specific CTLs that suppressed tumor growth. Murine HSCs, which were genetically modified with chicken ovalbumin (OVA)-specific T cell receptor, were adoptively transferred into recipient mice. In the following week, mice were administered with intraperitoneal injections of an agonist α-Notch 2 antibody and cytokines (rFlt3L and rIL-7) three times. After another two weeks, mice received a subcutaneous inoculation of B16-OVA melanoma cells that express OVA as a surrogate tumor Ag, before the anti-tumor activity of HSC-derived T cells was assessed. OVA-specific CTLs developed in vivo and greatly responded to OVA Ag stimulation ex vivo. In addition, mice receiving genetically modified HSCs and in vivo priming established anti-tumor immunity, resulting in the suppression of tumor growth. These results reported in this present study provide an alternative strategy to develop protective cancer vaccines by using genetically modified HSCs. |
| first_indexed | 2024-04-13T06:43:41Z |
| format | Article |
| id | doaj.art-38f23f36b51a43d7a3a48cc83dad222f |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-13T06:43:41Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-38f23f36b51a43d7a3a48cc83dad222f2022-12-22T02:57:40ZengMDPI AGVaccines2076-393X2018-07-01634010.3390/vaccines6030040vaccines6030040Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem CellsXiaofang Xiong0Jugal Kishor Das1Jianyong Song2Bing Ni3Xingcong Ren4Jin-Ming Yang5Jianxun Song6Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, College Station, TX 77843, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, College Station, TX 77843, USAInstitutes of Irradiation/Immunology, The Third Military Medical University, Chongqing 400038, ChinaInstitutes of Irradiation/Immunology, The Third Military Medical University, Chongqing 400038, ChinaDepartment of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, College Station, TX 77843, USAHematopoietic stem cells (HSCs) yield both the myeloid and lymphoid lineages of blood cells and can be reprogrammed into tumor antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) to prevent tumor growth. However, the optimal approach for differentiating tumor Ag-specific CTLs from HSCs, such as HSC-CTLs, remains elusive. In the current study, we showed that a combination of genetic modification of HSCs and in vivo T cell development facilitates the generation of Ag-specific CTLs that suppressed tumor growth. Murine HSCs, which were genetically modified with chicken ovalbumin (OVA)-specific T cell receptor, were adoptively transferred into recipient mice. In the following week, mice were administered with intraperitoneal injections of an agonist α-Notch 2 antibody and cytokines (rFlt3L and rIL-7) three times. After another two weeks, mice received a subcutaneous inoculation of B16-OVA melanoma cells that express OVA as a surrogate tumor Ag, before the anti-tumor activity of HSC-derived T cells was assessed. OVA-specific CTLs developed in vivo and greatly responded to OVA Ag stimulation ex vivo. In addition, mice receiving genetically modified HSCs and in vivo priming established anti-tumor immunity, resulting in the suppression of tumor growth. These results reported in this present study provide an alternative strategy to develop protective cancer vaccines by using genetically modified HSCs.http://www.mdpi.com/2076-393X/6/3/40hematopoietic stem cellsT cellsimmunotherapymelanomamouse model |
| spellingShingle | Xiaofang Xiong Jugal Kishor Das Jianyong Song Bing Ni Xingcong Ren Jin-Ming Yang Jianxun Song Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells Vaccines hematopoietic stem cells T cells immunotherapy melanoma mouse model |
| title | Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells |
| title_full | Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells |
| title_fullStr | Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells |
| title_full_unstemmed | Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells |
| title_short | Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells |
| title_sort | protective cancer vaccine using genetically modified hematopoietic stem cells |
| topic | hematopoietic stem cells T cells immunotherapy melanoma mouse model |
| url | http://www.mdpi.com/2076-393X/6/3/40 |
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