Prevention of hepatic tumor metastases in rats with herpes viral vaccines and γ-interferon

Howard M. Karpoff, Michael D'Angelica, Sarah Blair, Michael D. Brownlee, Howard Federoff, Yuman Fong

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)799-804
Number of pages6
JournalJournal of Clinical Investigation
Volume99
Issue number4
StatePublished - Feb 15 1997

Fingerprint

Viral Vaccines
Interferons
Granulocyte-Macrophage Colony-Stimulating Factor
Neoplasm Metastasis
Liver
Interleukin-2
Neoplasms
Kupffer Cells
Macrophages
Lymphocytes
Immunosuppressive Agents
Hepatocellular Carcinoma
Growth
Active Immunotherapy
Hepatectomy
Therapeutics
Lymphocyte Activation
Vaccination
Vaccines

Keywords

  • GM-CSF
  • hepatectomy
  • HSV
  • IL-2
  • liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Karpoff, H. M., D'Angelica, M., Blair, S., Brownlee, M. D., Federoff, H., & Fong, Y. (1997). Prevention of hepatic tumor metastases in rats with herpes viral vaccines and γ-interferon. Journal of Clinical Investigation, 99(4), 799-804.

Prevention of hepatic tumor metastases in rats with herpes viral vaccines and γ-interferon. / Karpoff, Howard M.; D'Angelica, Michael; Blair, Sarah; Brownlee, Michael D.; Federoff, Howard; Fong, Yuman.

In: Journal of Clinical Investigation, Vol. 99, No. 4, 15.02.1997, p. 799-804.

Research output: Contribution to journalArticle

Karpoff, HM, D'Angelica, M, Blair, S, Brownlee, MD, Federoff, H & Fong, Y 1997, 'Prevention of hepatic tumor metastases in rats with herpes viral vaccines and γ-interferon', Journal of Clinical Investigation, vol. 99, no. 4, pp. 799-804.
Karpoff HM, D'Angelica M, Blair S, Brownlee MD, Federoff H, Fong Y. Prevention of hepatic tumor metastases in rats with herpes viral vaccines and γ-interferon. Journal of Clinical Investigation. 1997 Feb 15;99(4):799-804.
Karpoff, Howard M. ; D'Angelica, Michael ; Blair, Sarah ; Brownlee, Michael D. ; Federoff, Howard ; Fong, Yuman. / Prevention of hepatic tumor metastases in rats with herpes viral vaccines and γ-interferon. In: Journal of Clinical Investigation. 1997 ; Vol. 99, No. 4. pp. 799-804.
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