RRC ID 44138
Author Shimizu K, Mizuno T, Shinga J, Asakura M, Kakimi K, Ishii Y, Masuda K, Maeda T, Sugahara H, Sato Y, Matsushita H, Nishida K, Hanada K, Dorrie J, Schaft N, Bickham K, Koike H, Ando T, Nagai R, Fujii S.
Title Vaccination with antigen-transfected, NKT cell ligand-loaded, human cells elicits robust in situ immune responses by dendritic cells.
Journal Cancer Res.
Abstract Both innate and adaptive immunity are crucial for cancer immunosurveillance, but precise therapeutic equations to restore immunosurveillance in patients with cancer patients have yet to be developed. In murine models, α-galactosylceramide (α-GalCer)-loaded, tumor antigen-expressing syngeneic or allogeneic cells can act as cellular adjuvants, linking the innate and adaptive immune systems. In the current study, we established human artificial adjuvant vector cells (aAVC) consisting of human HEK293 embryonic kidney cells stably transfected with the natural killer T (NKT) immune cell receptor CD1d, loaded with the CD1d ligand α-GalCer and then transfected with antigen-encoding mRNA. When administered to mice or dogs, these aAVC-activated invariant NKT (iNKT) cells elicited antigen-specific T-cell responses with no adverse events. In parallel experiments, using NOD/SCID/IL-2rγc(null)-immunodeficient (hDC-NOG) mouse model, we also showed that the human melanoma antigen, MART-1, expressed by mRNA transfected aAVCs can be cross-presented to antigen-specific T cells by human dendritic cells. Antigen-specific T-cell responses elicited and expanded by aAVCs were verified as functional in tumor immunity. Our results support the clinical development of aAVCs to harness innate and adaptive immunity for effective cancer immunotherapy.
Volume 73(1)
Pages 62-73
Published 2013-1-1
DOI 10.1158/0008-5472.CAN-12-0759
PII 0008-5472.CAN-12-0759
PMID 23108144
MeSH Adaptive Immunity / immunology Animals Antigens, Neoplasm / immunology* Cancer Vaccines / immunology* Cross-Priming / immunology Dendritic Cells / immunology* Dogs Flow Cytometry HEK293 Cells Humans Immunity, Innate / immunology Lymphocyte Activation / immunology Mice Mice, Inbred C57BL Natural Killer T-Cells / immunology* Natural Killer T-Cells / transplantation* Transfection
IF 9.13
Times Cited 12
Human and Animal Cells