Enhancement of anti-tumor immune responses by transfection of IFNγ gene into tumor using a novel type synthetic vector

The existence of Th1 responses in a tumor microenvironment elicits a better prognosis for the patients. Transfection of Th1 polarizing cytokines, such as IFN gamma, into tumor cells is an effective way to set up an appropriate microenvironment. Using a novel type synthetic vector composed of polyamidoamine dendrons, we transfected canine IFN gamma gene into canine tumor cell lines, and examined direct and indirect effects of dendritic cells (DCs) against tumor growth in vitro. A cloned canine IFN gamma gene expressed functional protein that induces maturation of DCs. When the canine IFN gamma gene was transfected into canine tumor cell lines using the synthetic vector, most cells secreted canine IFN gamma. Secretion of IFN gamma reduced with time, but was maintained for 48 h. DCs incubated with the IFN gamma-transfected tumor cells exhibited greater suppressive activity and induced significantly higher cytotoxic activity against the tumor cells, relative to those incubated with untransfected tumor cells and comparable dose of IFN gamma. Successful transfection of IFN gamma by the synthetic vector efficiently enhanced the antitumor immune function of DCs, and sets up a suitable microenvironment for improvement in tumor therapy. (C) 2014 Elsevier B.V. All rights reserved.