Prevention of hepatic tumor metastases in rats with herpes viral vaccines and γ-interferon Journal Article
| Authors: | Karpoff, H. M.; D'Angelica, M.; Blair, S.; Brownlee, M. D.; Federoff, H.; Fong, Y. |
| Article Title: | Prevention of hepatic tumor metastases in rats with herpes viral vaccines and γ-interferon |
| Abstract: | Previous studies showed that γIFN decreases metastatic hepatic tumor growth by stimulating Kupffer cells (KC). The present studies examine whether lymphocyte stimulation via cells engineered to secrete GM-CSF or IL- 2 decreases hepatic tumor growth, and whether stimulation of both macrophages and lymphocytes is more effective than either individually. Rats were immunized with irradiated hepatoma cells transduced by herpes vital amplicon vectors containing the genes for GM-CSF, IL-2 or LacZ. On day 18, half of each group was treated with 5 x 104 U γIFN, or saline intraperitoneally for 3 d. On day 21, all rats received 5 x 105 hepatoma cells intrasplenically. On day 41, rats were killed and tumor nodules were counted. Separate rats underwent splenocyte and KC harvest for assessment of lymphocyte- and macrophage-mediated tumor cell kill in vitro. GM-CSF or IL- 2 vaccines or γIFN decreased tumor nodules significantly (GM-CSF 13±4, IL- 2 14±6 vs. control 75±24, P < 0.001). Combination therapy was more effective, and completely eliminated tumor in 4 of 12 IFN-GM-CSF and 8 of 11 IFN-IL-2 animals. Additional rats underwent partial hepatectomy, an immunosuppressive procedure known to accelerate the growth of hepatic tumor, following tumor challenge. Therapy was equally effective in this immunosuppressive setting. Vaccination is associated with enhancement of splenocyte-mediated tumoricidal activity, whereas the effect of γIFN is mediated by KC. GM-CSF and IL-2 vaccine therapy and pretreatment with γIFN represent effective strategies in reducing hepatic tumor. Combination therapy targets both lymphocytes and macrophages, and is more effective in reducing tumor than either therapy alone. |
| Keywords: | controlled study; nonhuman; animals; cell division; interleukin 2; spleen; granulocyte macrophage colony stimulating factor; animal model; liver carcinoma; cancer inhibition; liver; cytokines; genetic transfection; gamma interferon; rat; neoplasm metastasis; simplexvirus; hepatectomy; kupffer cell; immunomodulation; rats; viral vaccines; partial hepatectomy; il-2; gm-csf; cytotoxicity tests, immunologic; cancer immunology; metastasis inhibition; interferon type ii; intraperitoneal drug administration; liver neoplasms, experimental; hsv; kupffer cells; male; priority journal; article; rats, inbred buf; herpes vaccine |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 99 |
| Issue: | 4 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 1997-02-15 |
| Start Page: | 799 |
| End Page: | 804 |
| Language: | English |
| PUBMED: | 9045885 |
| PROVIDER: | scopus |
| PMCID: | PMC507865 |
| DOI: | 10.1172/JCI119226 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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777D'Angelica
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