Biodistribution and tumor infectivity of semliki forest virus vectors in mice: effects of re-administration
Rodriguez-Madoz JR, Prieto J, Smerdou C.
Division of Gene Therapy, School of Medicine, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
Semliki Forest virus (SFV)-based vectors have broad tropism, with the ability to infect cells from various origins, including those from tumors.
These vectors express cytokines after intra-tumoral (IT) injection, and have therefore been used for inducing efficient anti-tumoral responses in several tumor models. We were interested in studying whether SFV vectors could escape from tumors after IT injection and whether they could target tumors if administered systemically. We analyzed the biodistribution of an SFV vector expressing luciferase (SFV-Luc) after intravenous (IV), intraperitoneal (IP), and IT administration in immunocompetent mice. SFV-Luc systemic inoculation led to high infectivity in heart and lung, and moderate levels of infectivity in spleen, kidney, and gonads, without gender being a factor in the outcome.
Tumor-specific infection, without the vector spreading to other tissues, was achieved only by IT inoculation. We also investigated the effect of SFV pre-inoculation on subsequent vector administrations. Systemic inoculation with one dose of 10(7) vp (viral particles), or two doses of 10(6) vp of SFV-LacZ given with a 20-day interval between the doses, was able to strongly inhibit luciferase expression in animals re-inoculated systemically with SFV-Luc, correlating with high sera neutralizing antibodies titers. However, IT pre-inoculation with 10(8) vp of SFV-LacZ impaired tumor re-infection only moderately, thereby indicating that tumors can be treated with several doses of SFV vectors.
CITATION Mol Ther. 2007 Dec;15(12):2164-71