In vivo cancer gene therapy with a recombinant interleukin-2 adenovirus vector

Cancer Gene Ther. Jan-Feb 1996;3(1):11-7.

Abstract

Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. In vivo therapy of established murine fibrosarcoma and mammary carcinomas was attempted with intratumoral injections of a recombinant AdV vector in which the human interleukin-2 (IL-2) gene was driven by the cytomegalovirus enhancer/promoter. Delayed growth and rejection of some tumors could be achieved with a cumulative virus dose of 2 to 6 x 10(9) plaque-forming units in two or three divided doses. Lower viral doses were ineffective, and higher doses resulted in animal death due to IL-2 toxicity. Using AdV vectors with the marker genes beta-galactosidase and luciferase, it is clear that even small volume (10 to 20 microL) intratumoral injections result in substantial systemic delivery of a portion of the virus dose. These findings define the potential and limitations of in vivo AdV-based cancer gene therapy and provide support for strategies to develop tumor-specific vectors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Enhancer Elements, Genetic
  • Fibrosarcoma / genetics
  • Fibrosarcoma / pathology
  • Fibrosarcoma / therapy
  • Gene Expression
  • Gene Transfer Techniques
  • Genes, Reporter
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Humans
  • Interleukin-2 / genetics*
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / therapy
  • Mice
  • Mice, Inbred C3H
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy*
  • Promoter Regions, Genetic
  • Tumor Cells, Cultured

Substances

  • Interleukin-2