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Vaccines 2018, 6(3), 40; https://doi.org/10.3390/vaccines6030040

Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells

1
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, College Station, TX 77843, USA
2
Institutes of Irradiation/Immunology, The Third Military Medical University, Chongqing 400038, China
3
Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
*
Author to whom correspondence should be addressed.
Received: 30 May 2018 / Revised: 26 June 2018 / Accepted: 5 July 2018 / Published: 6 July 2018
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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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. View Full-Text
Keywords: hematopoietic stem cells; T cells; immunotherapy; melanoma; mouse model hematopoietic stem cells; T cells; immunotherapy; melanoma; mouse model
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Xiong, X.; Das, J.K.; Song, J.; Ni, B.; Ren, X.; Yang, J.-M.; Song, J. Protective Cancer Vaccine Using Genetically Modified Hematopoietic Stem Cells. Vaccines 2018, 6, 40.

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