Effects of Survivin Antagonists on Growth of Established Tumors and B7-1 Immunogene Therapy

Abstract

Background: Survivin, a member of the inhibitor of apopto-sis (IAP) protein family, is detectable in most types of cancer, and its presence is associated with a poor prognosis. We determined the effects of gene-based therapies that inhibit survivin function in a mouse tumor model. Methods: Using five to six mice per treatment group, we injected tumors derived from mouse EL-4 thymic lymphoma cells with plas-mids encoding antisense survivin, a dominant-negative mu-tant survivin, and the T-cell costimulator B7-1. Expression of endogenous survivin and the proteins encoded by the in-jected plasmids were examined by immunohistochemical staining of tumor sections and by western blot and flow cytometry analyses of isolated tumor cells. Tumor growth, the generation of antitumor cytotoxic T-lymphocyte (CTL) activity, apoptosis, and the contribution of leukocyte subsets