Postoperative immuno-gene therapy of murine bladder tumor by in vivo administration of retroviruses expressing mouse interferon-γ

Abstract

The murine MBT-2 bladder tumor model in syngeneic C₃H/HeN mice was used to investigate the feasibility of gene therapy based on the delivery of interferon-γ (IFN-γ) in vivo by retroviral vectors. We constructed a recombinant retroviral vector pRUFneo/IFN-γ, which was transfected into a retroviral packaging cell line ψCRE, to produce ψCRE/pRUFneo/IFN-γ cells. The expressions of the neo and IFN-γ genes were verified by reverse transcription-polymerase chain reaction and IFN-γ was detected in the culture supernatant from ψCRE/pRUFneo/IFN-γ cells. After receiving MBT-2 cells admixed with retroviral pRUFneoIFN-γ supernatant, C₃H/HeN mice exhibited lower tumor incidence, lower tumor mass, and higher survival rate, as well as higher antitumor responses compared to those injected with MBT-2 cells admixed with control retroviral supernatant. Moreover, the retroviral pRUFneoIFN-γ supernatant was able to suppress the growth of rechallenged tumors in postoperated mice. Although the IFN-γ protein secreted from ψCRE/pRUFneo/IFN-γ cells partly contributes to the antitumor effect of retroviral pRUFneoIFN-γ supernatant, the retroviruses carrying the IFN-γ gene transduced MBT-2 cells in vivo, which may result in enhancing local IFN-γ production from tumor cells. Because bladder is suitable for the intravesical instillation of therapeutic agents, in vivo administration of retroviral vectors encoding IFN-γ may be explored for the treatment of bladder cancer. Cancer Gene Therapy (2001) 8, 73–81