Combination gene therapy of IL-12 and allogeneic MHC class I gene via stimulating NK cytolytic activity.
In this study, we tested whether expressing an allogeneic MHC class I gene and/or a cytokine gene in tumor cells could induce anti-tumor immunity. We compared the potential therapeutic benefit of introducing IL-12 or H-2Kb alone and in combination into CT26 tumor cells. Whereas IL-12 expression in CT26 cells delayed the formation of tumors, the expression of class I molecules alone was apparently insufficient to reduce tumorigenicity. The combined expression of IL-12 and H-2Kb, however, more efficiently reduced tumor growth than did either genes alone. Histological examination of tumors expressing IL-12 and H-2Kb showed a non-specific inflammatory reaction, such as a necrosis, and an increased tissue infiltrate of immune effectors. These results suggest that the combined expression of IL-12 and H-2Kb in tumor cells has potential therapeutic benefit.
Yoon
S J
SJ
Department of Internal Medicine, Seoul National University Hospital, Korea.
Heo
D S
DS
Kang
J O
JO
Kim
N K
NK
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000818:Animals; D015152:Blotting, Northern; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006183:H-2 Antigens / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D008081:Liposomes; D018664:Interleukin-12