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- Title
Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells.
- Authors
Xiong, Xiaofang; Das, Jugal Kishor; Song, Jianyong; Ni, Bing; Ren, Xingcong; Yang, Jin-Ming; Song, Jianxun
- Abstract
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.
- Subjects
CANCER vaccines; HEMATOPOIETIC stem cells; LYMPHOID tissue; TUMOR antigens; T cells
- Publication
Vaccines, 2018, Vol 6, Issue 3, p40
- ISSN
2076-393X
- Publication type
Article
- DOI
10.3390/vaccines6030040