Neoadjuvant interleukin-12 immunogene therapy protects against cancer recurrence after liver resection in an animal model Journal Article
| Authors: | Jarnagin, W. R.; Delman, K.; Kooby, D.; Mastorides, S.; Zager, J.; Brennan, M. F.; Blumgart, L. H.; Federoff, H.; Fong, Y. |
| Article Title: | Neoadjuvant interleukin-12 immunogene therapy protects against cancer recurrence after liver resection in an animal model |
| Abstract: | Objective: To evaluate the neoadjuvant use of a herpes simplex viral (HSV) amplicon vector expressing the murine interleukin-12 (IL-12) gene. Summary Background Data: Surgery is the most effective therapy for hepatic malignancy. Recurrences, which are common, most often occur in the remnant liver and are due partly to growth of residual microscopic disease in the setting of postoperative host cellular immune dysfunction. The authors hypothesized that engineering tumors to secrete IL-12 in vive would elicit an immune response directed at residual tumor and would reduce the incidence of recurrence after resection. Methods: Solitary hapatomas were established in Buffalo rat livers and directly injected with 106 particles of HSV carrying the gene for IL-12, lacZ (β-galactosidase) or with saline. One week after injection, the animals were challenged with an intraportal injection of 106 tumor cells, with subsequent resection of the hepatic lobe containing the previously established macroscopic tumor nodule, recreating the clinical scenario of residual microscopic cancer. Results: Hepatoma cells transfected with HSV-IL-12 produced high levels of IL-12 in vitro and in vivo. A significant local immune response developed, as evidenced by a progressive increase in the number of CD4(+) and CD8(+) lymphocytes in the tumor. Treatment of established hepatomas with HSV-IL-12 protected against growth of microscopic residual cancer after hepatic resection. Sixty-four percent of the animals treated with HSV-IL-12 had zero or one tumors compared with 30% of HSVlac-treated and 24% of saline-treated animals. Conclusions: This neoadjuvant immune strategy may prove useful in reducing the incidence of cancer recurrence after hepatic resection. |
| Keywords: | immunohistochemistry; controlled study; protein expression; cancer recurrence; liver cell carcinoma; nonhuman; adjuvant therapy; animals; cancer prevention; neoplasm recurrence, local; animal experiment; animal model; genetic vectors; immune response; rat; gene therapy; beta galactosidase; simplexvirus; liver resection; hepatectomy; rats; herpes simplex virus; interleukin 12; beta-galactosidase; interleukin-12; liver neoplasms, experimental; male; priority journal; article; rats, inbred buf |
| Journal Title: | Annals of Surgery |
| Volume: | 231 |
| Issue: | 5 |
| ISSN: | 0003-4932 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2000-05-01 |
| Start Page: | 762 |
| End Page: | 771 |
| Language: | English |
| DOI: | 10.1097/00000658-200005000-00017 |
| PUBMED: | 10767798 |
| PROVIDER: | scopus |
| PMCID: | PMC1421064 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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