Elsevier

Surgery

Volume 118, Issue 2, August 1995, Pages 185-191
Surgery

In vivo gene therapy of a murine pancreas tumor with recombinant vaccinia virus encoding human interleukin-1beta*

https://doi.org/10.1016/S0039-6060(05)80322-8Get rights and content

Background. Recombinant vaccinia virus (VV) encoding human interleukin-1β (vMJ601hIL-1β) given intravenously persists in tumor tissue and expresses hIL-1β for at least 9 days after treatment and is associated with significant retardation of tumor growth. To document the significance of this approach and to further elucidate the mechanism, this study compares the antitumor effect of vMJ601hIL-1β administered either intravenously or intratumorally and intravenous recombinant hIL-1β protein.

Methods. C57BL/6 mice with established subcutaneous pancreatic tumors were randomized to treatment with intravenous or intratumoral vMJ601hIL-1β, wild-type VV, saline solution, or intravenous recombinant hIL-1β protein in a blinded fashion. Toxicity and tumor size were measured. Data were analyzed with the Kruskal-Wallis and Wilcoxon tests.

Results. Treatment with intratumoral vMJ601hIL-1β repeatedly resulted in significant reduction in tumor size as compared with saline treated controls (p<0.001). Tumor growth inhibition was consistently similar after intravenous or intratumoral vMJ601hIL-1β administration (p>0.52). Wild-type VV given intratumorally or intravenously had no antitumor effect versus saline controls (p>0.30). No significant toxicity or deaths resulted from vMJ601hIL-1β treatment. Recombinant hIL-1β protein administered intravenously caused severe toxicity (median lethal dose ≈ 100 μg/kg), and no significant antitumor effect was observed at sublethal doses versus saline controls (p=0.19).

Conclusions. Direct, in vivo hIL-1β gene delivery and expression by recombinant VV given intravenously or intratumorally results in significant tumor growth inhibition, which appears to be a consequence of local, intratumoral vaccinia infection and production of hIL-1β.

References (25)

  • YoungPR et al.

    Human interleukin 1β is not secreted from hamster fibroblasts when expressed constitutively from a transfected cDNA

    J Cell Biol

    (1988)
  • SaitoS et al.

    Immunotherapy of bladder cancer with cytokine gene-modified tumor vaccines

    Cancer Res

    (1994)
  • Cited by (0)

    *

    Presented at the Fifty-sixth Annual Meeting of the Society of University Surgeons, Denver, Colo., Feb. 9–11, 1995.

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