CD46 represents a target for adenoviral gene therapy of malignant glioma

Hum Gene Ther. 2006 May;17(5):556-64. doi: 10.1089/hum.2006.17.556.


Malignant gliomas remain refractory to adenovirus serotype 5 (Ad5) gene therapy because of the lack of the primary adenoviral receptor, the coxsackie-adenovirus receptor (CAR), on tumor cells. To bypass the dependence on CAR, we investigated the expression of adenovirus serotype 3 (Ad3) receptor, or CD46, on glioma cells. First, we analyzed the expression of CD46 by RT-PCR on primary and passaged glioma cells. We then performed immunofluorescence studies to examine protein expression of CAR and CD46 on the same tumor lines. Finally, we constructed a replication-defective Ad vector that binds to CD46 and contains a luciferase transgenic cassette in place of the deleted E1 region: Ad5/3 (containing tail/shaft domain of Ad5 and knob domain of Ad3). These vectors were analyzed in vitro and in vivo against malignant glioma and compared with wild-type Ad5 or control vector Ad3/5 (containing tail of Ad5, shaft of Ad3, and knob of Ad5). The chimeric vector Ad5/3 showed a significant increase in the transduction efficiency of glioma tumor cells. At the same time, blocking the CD46 receptor caused a 65% inhibition of adenoviral infection when using Ad5/3. Taken together, these results indicate that CD46 is overexpressed by malignant glioma. Retargeting to the Ad3 receptor enhances gene transfer and offers a novel target for gene therapy of malignant brain tumors.

Publication types

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

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cell Line, Tumor
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Gene Expression Profiling
  • Genetic Therapy*
  • Genetic Vectors
  • Glioma / therapy*
  • Humans
  • Membrane Cofactor Protein / genetics*
  • Membrane Cofactor Protein / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Virus / genetics


  • CD46 protein, human
  • CLMP protein, human
  • CLMP protein, mouse
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Membrane Cofactor Protein
  • Receptors, Virus