Enhanced tumor suppressor gene therapy via replication-deficient adenovirus vectors expressing an N-terminal truncated retinoblastoma protein

Cancer Res. 1996 May 15;56(10):2245-9.

Abstract

The preclinical studies presented here demonstrate that treatment of human non-small cell lung carcinoma and bladder carcinoma cells by a recombinant adenovirus vector, AdCMVpRB94, expressing the N-terminal truncated retinoblastoma (RB) protein (pRB94) completely suppressed the tumorigenicity of the treated tumor cells in nude mice. Furthermore, gene therapy of established human RB- and RB+ bladder xenograft cancers in nude mice by AdCMVpRB94 resulted in regression of the treated tumors. Of note, although both the full-length and the truncated forms of the RB protein, when overexpressed in tumor cells via replication-deficient adenovirus vectors, were capable of suppression of tumor growth, the pRB94 was evidently more potent than the full-length RB protein.

Publication types

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

MeSH terms

  • Adenoviruses, Human / genetics*
  • Adenoviruses, Human / physiology
  • Animals
  • Bone Neoplasms / pathology
  • Breast Neoplasms / pathology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / therapy*
  • DNA Replication
  • DNA, Complementary / genetics
  • Defective Viruses / genetics*
  • Defective Viruses / physiology
  • Genes, Retinoblastoma*
  • Genetic Therapy*
  • Genetic Vectors / genetics*
  • Humans
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Osteosarcoma / pathology
  • Peptide Fragments / genetics*
  • Retinoblastoma Protein / biosynthesis
  • Retinoblastoma Protein / chemistry
  • Retinoblastoma Protein / genetics*
  • Sequence Deletion
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*
  • Virus Replication

Substances

  • DNA, Complementary
  • Peptide Fragments
  • Retinoblastoma Protein