Protective cancer vaccine using genetically modified hematopoietic stem cells

Xiaofang Xiong, Jugal Kishor Das, Jianyong Song, Bing Ni, Xingcong Ren, Jin-Ming Yang, Jianxun Song

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number40
JournalVaccines
Volume6
Issue number3
DOIs
StatePublished - Sep 1 2018

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Cancer Vaccines
Hematopoietic Stem Cells
Ovalbumin
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Neoplasms
Growth
T-Lymphocytes
Antigens
Experimental Melanomas
T-Cell Antigen Receptor
Intraperitoneal Injections
Chickens
Immunity
Blood Cells
Cytokines
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Xiong, X., Das, J. K., Song, J., Ni, B., Ren, X., Yang, J-M., & Song, J. (2018). Protective cancer vaccine using genetically modified hematopoietic stem cells. Vaccines, 6(3), [40]. https://doi.org/10.3390/vaccines6030040
Xiong, Xiaofang ; Das, Jugal Kishor ; Song, Jianyong ; Ni, Bing ; Ren, Xingcong ; Yang, Jin-Ming ; Song, Jianxun. / Protective cancer vaccine using genetically modified hematopoietic stem cells. In: Vaccines. 2018 ; Vol. 6, No. 3.
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Xiong, X, Das, JK, Song, J, Ni, B, Ren, X, Yang, J-M & Song, J 2018, 'Protective cancer vaccine using genetically modified hematopoietic stem cells', Vaccines, vol. 6, no. 3, 40. https://doi.org/10.3390/vaccines6030040

Protective cancer vaccine using genetically modified hematopoietic stem cells. / Xiong, Xiaofang; Das, Jugal Kishor; Song, Jianyong; Ni, Bing; Ren, Xingcong; Yang, Jin-Ming; Song, Jianxun.

In: Vaccines, Vol. 6, No. 3, 40, 01.09.2018.

Research output: Contribution to journalArticle

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AU - Xiong, Xiaofang

AU - Das, Jugal Kishor

AU - Song, Jianyong

AU - Ni, Bing

AU - Ren, Xingcong

AU - Yang, Jin-Ming

AU - Song, Jianxun

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