Oncolytic Potential of E1B 55 kDa-deleted YKL-1 Recombinant Adenovirus: Correlation With p53 Functional Status

Int J Cancer. 2000 Nov 1;88(3):454-63. doi: 10.1002/1097-0215(20001101)88:3<454::aid-ijc19>3.0.co;2-t.

Abstract

YKL-1, E1B 55 kDa-deleted recombinant adenovirus vector, capable of harboring a transgene casette of up to 4.9 kb, was newly constructed by reintroducing E1A and E1B 19 kDa into E1/E3-deleted adenoviral vector with a homologous recombination in E. coli. Virus replication and cytotoxicity were dramatically attenuated in all 3 different types of normal human cells. In contrast, YKL-1 efficiently replicated and induced cytotoxicity in most cancer cells, especially Hep3B and C33A cells with an inactivating p53 mutation. However, both H460 and HepG2 exhibited intermediate sensitivity to YKL-1, which was between that of Hep3B or C33A and normal human cells. The YKL-1 and DNA damaging agent, camptothecin effectively induced p53 in H460 and HepG2 as well as in normal cells. Furthermore, YKL-1 effectively prohibited both Hep3B and C33A tumor growth in nu/nu mice in a dose-dependent manner. H/E staining and TUNEL assay indicated a largely distributed necrotic area and apoptosis on its periphery. This study, therefore, indicates that YKL-1, possesses promising potential as an oncolytic adenoviral vector, which acts partially in a p53-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / physiology*
  • Adenovirus E1B Proteins / physiology*
  • Animals
  • Cell Line
  • Cytopathogenic Effect, Viral
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Molecular Weight
  • Neoplasm Transplantation
  • Neoplasms, Experimental / therapy*
  • Recombination, Genetic
  • Transplantation, Heterologous
  • Tumor Suppressor Protein p53 / physiology*
  • Virus Replication

Substances

  • Adenovirus E1B Proteins
  • Tumor Suppressor Protein p53