Postoperative immuno-gene therapy of murine bladder tumor by in vivo administration of retroviruses expressing mouse interferon-gamma.
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-gamma (IFN-gamma) in vivo by retroviral vectors. We constructed a recombinant retroviral vector pRUFneo/IFN-gamma, which was transfected into a retroviral packaging cell line psiCRE, to produce psiCRE/pRUFneo/IFN-gamma cells. The expressions of the neo and IFN-gamma genes were verified by reverse transcription-polymerase chain reaction and IFN-gamma was detected in the culture supernatant from psiCRE/pRUFneo/IFN-gamma cells. After receiving MBT-2 cells admixed with retroviral pRUFneoIFN-gamma 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-gamma supernatant was able to suppress the growth of rechallenged tumors in postoperated mice. Although the IFN-gamma protein secreted from psiCRE/pRUFneo/IFN-gamma cells partly contributes to the antitumor effect of retroviral pRUFneoIFN-gamma supernatant, the retroviruses carrying the IFN-gamma gene transduced MBT-2 cells in vivo, which may result in enhancing local IFN-gamma production from tumor cells. Because bladder is suitable for the intravesical instillation of therapeutic agents, in vivo administration of retroviral vectors encoding IFN-gamma may be explored for the treatment of bladder cancer.
Shiau
A L
AL
Department of Microbiology, National Cheng Kung University Medical College, Tainan, Taiwan.
Lin
C Y
CY
Tzai
T S
TS
Wu
C L
CL
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002857:Chromium / Q000032:analysis / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000378:metabolism; D019868:Kanamycin Kinase / Q000235:genetics / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D008415:Mastocytosis / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011182:Postoperative Care; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology
D017931:DNA Primers; D007376:Interleukin-2; D012367:RNA, Viral; D011994:Recombinant Proteins; D002857:Chromium; D007371:Interferon-gamma; D019868:Kanamycin Kinase