GENE-TRANSFER INTO EXPERIMENTAL BRAIN-TUMORS MEDIATED BY ADENOVIRUS, HERPES-SIMPLEX VIRUS, AND RETROVIRUS VECTORS

Three vectors derived from retrovirus, herpes simplex virus type 1 (HS V), and adenovirus were compared in cultured rat 9L gliosarcoma cells for gene transfer efficiency and in a 9L, rat brain tumor model for hi stologic pattern and distribution of foreign gene delivery, as well as for associated tumor necrosis and inflammation. At a multiplicity of infection of 1, in vitro transfer of a foreign gene (lacZ from Escheri chia coil) into cells was more efficient with either the replication-d efective retrovirus vector or the replication-conditional thymidine ki nase (TK)-deficient HSV vector than with the replication-defective ade novirus vector. In vivo, stereotactic injections of each vector into r at brain tumors revealed three main histopathologic findings: (i) retr ovirus and HSV vector-mediated gene transfer was relatively selective for cells within the tumor, whereas adenovirus vector-mediated gene tr ansfer occurred into several types of endogenous neural cells, as well as into cells within the tumor; (ii) gene transfer to multiple infilt rating tumor deposits without apparent gene transfer to intervening no rmal brain tissue occurred uniquely in one animal inoculated with the HSV vector, and (iii) extensive necrosis and selective inflammation in the tumor were evident with the HSV vector, whereas there was minimal evidence of tumor necrosis and inflammation with either the retroviru s or adenovirus vectors.