RRC ID 50647
Author Kitadani J, Ojima T, Iwamoto H, Tabata H, Nakamori M, Nakamura M, Hayata K, Katsuda M, Miyajima M, Yamaue H.
Title Cancer Vaccine Therapy Using Carcinoembryonic Antigen - expressing Dendritic Cells generated from Induced Pluripotent Stem Cells.
Journal Sci Rep
Abstract Clinical application of dendritic cell (DC) vaccine therapy is hindered by the need for a large quantity of DCs generated from peripheral blood monocytes of the patient. We investigated whether genetically modified human induced pluripotent stem cell (iPSC)-derived dendritic cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce CEA-specific cytotoxic T cells in a human model and whether genetically modified mouse iPSDCs (miPSDCs) expressing CEA showed an actual antitumor effect using a CEA transgenic mouse model. We differentiated hiPSDCs from iPSCs of three healthy donors and transduced CEA cDNA into the hiPSDCs. The surface marker expression, cytokine secretion and migratory capacity of the hiPSDCs were equivalent to those of human monocyte-derived DCs (hMoDCs). Cytotoxic T cells activated by hiPSDCs-CEA exhibited CEA-specific cytotoxic activity against the target cells expressing CEA. Furthermore, in the CEA transgenic mouse model, cytotoxic T cells activated in mice immunized with miPSDCs-CEA displayed CEA-specific cytotoxic activity against MC38-CEA. In the subcutaneous tumour model, vaccination with miPSDCs-CEA achieved a significant growth inhibitory effect on MC38-CEA. No adverse events caused by the administration of miPSDCs were observed. Genetic modification of iPSDCs, inducing the expression of CEA, is a promising tool for clinical applications of vaccine therapy for treating gastrointestinal cancer patients.
Volume 8(1)
Pages 4569
Published 2018-3-15
DOI 10.1038/s41598-018-23120-z
PII 10.1038/s41598-018-23120-z
PMID 29545628
PMC PMC5854614
MeSH Animals Cancer Vaccines / immunology* Carcinoembryonic Antigen / genetics Carcinoembryonic Antigen / immunology Carcinoembryonic Antigen / metabolism* Cells, Cultured Dendritic Cells / cytology Dendritic Cells / metabolism* Dendritic Cells / transplantation Humans Induced Pluripotent Stem Cells / cytology* Interferon-gamma / metabolism Interleukin-12 / metabolism Mice Mice, Inbred C57BL Mice, Transgenic Skin Neoplasms / immunology Skin Neoplasms / pathology Skin Neoplasms / prevention & control* Spleen / cytology T-Lymphocytes, Cytotoxic / immunology
IF 3.998
Times Cited 7
Human and Animal Cells iPS-MEF-Ng-20D-17(APS0001)