Replication-competent retrovirus vectors for cancer gene therapy

Chien K. Tai, Noriyuki Kasahara

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Oncolytic virotherapy represents an emerging field with tremendous promise for harnessing the replicative capabilities of viruses against rapidly proliferating cancer cells. Among the different replicating virus technologies being tested, replication-competent retrovirus (RCR) vectors based on murine leukemia virus (MLV) exhibit unique characteristics. MLV exhibits intrinsic tumor selectivity due to its inability to infect quiescent cells, and can achieve highly selective and stable gene transfer throughout entire solid tumors in vivo at efficiencies of up to >99%, even after initial inoculation at MOIs as low as 0.01. RCR vectors with suicide genes mediate synchronized cell killing after prodrug administration, and due to their ability to undergo stable integration, residual cancer cells serve as a reservoir for long-term viral persistence even as they migrate to new sites, enabling multiple cycles of prodrug to achieve prolonged survival benefit. Further testing in various tumor models, new vector targeting and delivery strategies, and development of GMP manufacturing, are being pursued through a multi-national consortium, and preparations are now being undertaken for clinical trials using RCR vectors in glioblastoma.

Original languageEnglish (US)
Pages (from-to)3083-3095
Number of pages13
JournalFrontiers in Bioscience
Volume13
Issue number8
DOIs
StatePublished - 2008
Externally publishedYes

Fingerprint

Gene therapy
Neoplasm Genes
Retroviridae
Viruses
Genetic Therapy
Tumors
Murine Leukemia Viruses
Cells
Prodrugs
Neoplasms
Oncolytic Virotherapy
Gene transfer
Aptitude
Residual Neoplasm
Glioblastoma
Suicide
Genes
Clinical Trials
Technology
Efficiency

Keywords

  • Replication
  • Retrovirus
  • Review
  • Suicide Gene
  • Vector
  • Virotherapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology
  • Medicine(all)

Cite this

Replication-competent retrovirus vectors for cancer gene therapy. / Tai, Chien K.; Kasahara, Noriyuki.

In: Frontiers in Bioscience, Vol. 13, No. 8, 2008, p. 3083-3095.

Research output: Contribution to journalArticle

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