title: Gene therapy for murine renal cell carcinoma using genetically engineered tumor cells to secrete interleukin-12.
abstract: To determine the possibility of gene therapy for renal cell carcinoma (RCC) using interleukin-12 (IL-12), we prepared genetically engineered murine RCC cells (Renca) which secrete IL-12 and evaluated the usefulness of these cells as a tumor vaccine. The IL-12 gene was transduced using MFG retroviral vector. The in vitro characteristics of transfectants--i.e., cell proliferation and expression of surface antigens--were then examined. In vivo tumorigenicity was assessed by subcutaneously injecting each type of cell in syngenic BALB/c mice. For the challenge experiments, the mice rejecting previously injected Renca IL-12 cells were rechallenged with parental cells. To determine the antitumor effect at remote sites, mice were injected with parental cells into the left flank, and then either Renca IL-12 or parental cells were inoculated into the opposite site on day 0 or 1. The transfected cells can secrete 146.7 ng/ml/10(6)cells/48 hr of IL-12, as confirmed here by bioassay. The in vitro characteristics of the transfectants were not altered, but in vivo tumorigenicity was significantly reduced. Of the 21 mice that rejected Renca IL-12 cells, 9 failed to develop tumors after the challenge with parental cells. In the mice treated with Renca IL-12 as a vaccine, both number and tumor volume of the mice that developed tumors at remote sites were reduced. IL-12 secreting Renca cells conferred both protective immunity to parental cells and delay of tumor growth at remote sites, indicating that IL-12 secreting Renca cells are a feasible candidate for use in gene therapy of RCC.
authors.affiliation: Department of Urology, Hiroshima University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kasaoka
authors.forename: T
authors.initials: T
authors.lastname: Nakamoto
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: H
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D018664:Interleukin-12 / Q000235:genetics* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018664:Interleukin-12