NDLI: Immunotherapy of radioresistant mammary tumors with early metastasis using molecular chaperone vaccines combined with ionizing radiation

Content Provider	PubMed Central
Author	Weng, Desheng Song, Baizheng Koido, Shigeo Calderwood, Stuart K. Gong, Jianlin
Abstract	In the present study, exposure of mammary tumor cells derived from mice transgenic for the polyomavirus middle T (PyMT) oncogene to ionizing radiation resulted in the generation of a tumor cell population that preferentially expressed cancer stem cell markers. In addition, these cells were more resistant to further radiation treatments and appeared to acquire enhanced capacity for dissemination to the lungs of mice. We therefore tested an immunotherapy approach to treatment of local and disseminated mammary tumor cells in a murine model, employing a recently developed molecular chaperone-based vaccine that specifically targets the radioresistant subpopulation of tumor cells. Heat shock protein 70-peptide complexes (Hsp70.PC-F) were extracted from fusions of dendritic cells (DC) and radiation enriched tumor cells and the resulting chaperone vaccines used to treat mice with pre-existing lung metastases. Immunization of mice with the Hsp70.PC-F vaccine resulted in a T-cell-mediated immune response including a significant increase in CD4 and CD8 T cell proliferations and the induction of effector T cells capable of targeting radioresistant tumor cells. Importantly, the growth of primary tumors was inhibited and the number of tumor cells metastasizing to lung significantly reduced by combining chaperone vaccine with radiotherapy. These results indicate that Hsp70.PC-F vaccine can induce specific immunity to radioresistant populations of mammary tumor cells and can thus compliment radiotherapy, leading to synergistic killing.
Related Links	http://dx.doi.org/10.4049/jimmunol.1203286
Ending Page	763
Page Count	9
Starting Page	755
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	2
Volume Number	191
Language	English
Publisher Date	2013-07-15
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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