TY - JOUR
T1 - Postoperative immuno-gene therapy of murine bladder tumor by in vivo administration of retroviruses expressing mouse interferon-γ
AU - Shiau, Ai Li
AU - Lin, Chih Yun
AU - Tzai, Tzong Shin
AU - Wu, Chao Liang
N1 - Funding Information:
We are indebted to Dr. T.J. Gonda (Hanson Center for Cancer Research, Adelaide, Australia ) and Dr. R.C. Mulligan (Whitehead Institute for Biomedical Research, Cambridge, USA) for providing pRUFneo and retroviral packaging cells, respectively. We thank P. Wu for critically reading the manuscript. This work was supported by g rants from the National Science Council (NSC87-2312-B006-005 and NSC87-2314-B006-122), Taiwan.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1038/sj.cgt.7700271
DO - 10.1038/sj.cgt.7700271
M3 - Article
C2 - 11219496
AN - SCOPUS:0035121668
SN - 0929-1903
VL - 8
SP - 73
EP - 81
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
IS - 1
ER -