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Dendritic Cells Transfected with a DNA Construct Encoding Tumour‐associated Antigen Epitopes Induce a Cytotoxic Immune Response Against Autologous Tumour Cells in a Culture of Mononuclear Cells from Colorectal Cancer Patients
Author(s) -
Kulikova E. V.,
Kurilin V. V.,
Shevchenko J. A.,
Obleukhova I. A.,
Khrapov E. A.,
Boyarskikh U. A.,
Filipenko M. L.,
Shorokhov R. V.,
Yakushenko V. K.,
Sokolov A. V.,
Sennikov S. V.
Publication year - 2015
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12311
Subject(s) - cytotoxic t cell , immune system , antigen , epitope , transfection , peripheral blood mononuclear cell , immunology , perforin , biology , ctl* , dendritic cell , cancer research , cd8 , cell culture , in vitro , biochemistry , genetics
Significant effort has been devoted to developing effective cancer vaccines based on dendritic cells ( DC s) loaded with various tumour antigens, including DNA constructs that carry sequences of tumour‐associated antigens ( TAA s). Such vaccines efficiently and selectively activate the T cell immune response. In this study, we describe a method to induce an antitumour immune response in mononuclear cell ( MNC ) cultures from colorectal cancer patients using DNA ‐transfected DC s encoding TAA epitopes of carcinoembryonic antigen, epithelial cell adhesion molecule and mucin 4. DC s were obtained from peripheral blood monocytes of colorectal cancer patients. Magnetic‐assisted transfection was used to deliver the genetic constructs to DC s. To assess the potency of the immune response, the antitumour cytotoxic response was assessed by lymphocyte intracellular perforin and the MNC cytotoxic activity against autologous tumour cells. We showed that polyepitope DNA ‐transfected DC s enhanced MNC antitumour activity, increasing tumour cell death and the percentage of perforin‐positive lymphocytes. In addition, DNA ‐transfected DC s elicited a cytotoxic response that was as efficient as that of tumour lysate‐loaded DC s. Taken together, the data suggest that it is feasible to induce an antitumour immune response in colorectal MNC s using transfected DC s. Thus, the DNA construct reported in this study may potentially be used in therapeutic and prophylactic DC ‐based vaccines.