Comparative effect of oncolytic adenoviruses with E1A or E1B-55 kDa deletions in malignant gliomas

Hong Jiang, Candelaria Gomez-Manzano, Ramon Alemany, Diana Medrano, Marta Alonso, B. Nebiyou Bekele, E. Lin, Charles C. Conrad, W. K.Alfred Yung, Juan Fueyo

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Replication-competent oncolytic adenoviruses hold considerable promise for treating malignant gliomas. The toxicity of the clinically tested E1B-55 kDa mutant virus is negligible; however, its full clinical potential is still being evaluated. The purpose of the present study is to compare the antiglioma activity in vitro and in vivo between Delta-24, an E1A mutant adenovirus, and RA55, an E1B-55 kDa mutant adenovirus. We selected human glioma cell lines that were tumorigenic in nude mice and express wild-type p53 (U-87 MG, D54 MG) or mutant p53(U-251 MG, U-373 MG) protein. Our studies demonstrated that Delta-24 induced a more potent antiglioma effect in vitro than RA55. Moreover, Delta-24 replicated markedly more efficiently than RA55 in both wild-type and mutant-p53 scenarios. Importantly, direct intratumoral injection of Delta-24, but not RA55, significantly suppresses tumor growth in intracranial (U-87 MG, U-251 MG) or subcutaneous (D54 MG) animal models. Staining for hexon protein detected replicating adenoviruses in xenografts infected with Delta-24, but not with RA55. Collectively, these data indicate that E1A mutant adenoviruses targeting the Rb pathway are more powerful putative agents for antiglioma therapy than E1B mutant adenoviruses, and suggest that E1A mutant adenoviruses should be tested in the clinical setting for patients with malignant gliomas.

Original languageEnglish (US)
Pages (from-to)48-56
Number of pages9
JournalNeoplasia
Volume7
Issue number1
DOIs
StatePublished - Jan 2005

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Adenoviridae
Glioma
Heterografts
Nude Mice
Proteins
Animal Models
Staining and Labeling
Viruses
Cell Line
Injections
Growth
Neoplasms

Keywords

  • E1A
  • E1B
  • Fiber protein
  • Glioma
  • Oncolytic adenovirus

ASJC Scopus subject areas

  • Cancer Research

Cite this

Comparative effect of oncolytic adenoviruses with E1A or E1B-55 kDa deletions in malignant gliomas. / Jiang, Hong; Gomez-Manzano, Candelaria; Alemany, Ramon; Medrano, Diana; Alonso, Marta; Bekele, B. Nebiyou; Lin, E.; Conrad, Charles C.; Yung, W. K.Alfred; Fueyo, Juan.

In: Neoplasia, Vol. 7, No. 1, 01.2005, p. 48-56.

Research output: Contribution to journalArticle

Jiang, Hong ; Gomez-Manzano, Candelaria ; Alemany, Ramon ; Medrano, Diana ; Alonso, Marta ; Bekele, B. Nebiyou ; Lin, E. ; Conrad, Charles C. ; Yung, W. K.Alfred ; Fueyo, Juan. / Comparative effect of oncolytic adenoviruses with E1A or E1B-55 kDa deletions in malignant gliomas. In: Neoplasia. 2005 ; Vol. 7, No. 1. pp. 48-56.
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