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Double-deleted vaccinia virus in virotherapy for refractory and metastatic pediatric solid tumors

Xueqing Lun1, Yibing Ruan, Aarthi Jayanthan

  • 1Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC) Laboratory for Pre-Clinical and Drug Discovery Studies, University of Calgary, Canada and Division of Pediatric Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada.

Molecular Oncology
|July 3, 2013
PubMed
Abstract

Insights

Double-deleted vaccinia virus (vvDD) effectively targets and destroys over 80% of pediatric solid tumor cells in vitro. Intravenous administration of vvDD significantly inhibited tumor growth and improved survival in preclinical models of difficult-to-treat pediatric cancers.

Area of Science:

  • Oncolytic virotherapy
  • Pediatric oncology
  • Viral gene therapy

Background:

  • Systemic double-deleted vaccinia virus (vvDD) has shown efficacy against adult cancers.
  • Pediatric solid tumors are challenging to treat with current therapies.

Purpose of the Study:

  • To evaluate the oncolytic potential of vvDD against pediatric solid tumor cell lines.
  • To assess vvDD efficacy in preclinical models of pediatric malignancies.

Main Methods:

  • Tested vvDD cytotoxicity against pediatric tumor cell lines (AT/RT, sarcoma, neuroblastoma) and normal fibroblasts in vitro.
  • Administered intravenous vvDD to xenograft models (intracranial, subcutaneous, metastatic) and assessed tumor growth, viral replication, and survival.

Main Results:

  • vvDD infected and killed 81.8% of tested pediatric tumor cell lines in vitro.
  • Intravenous vvDD significantly inhibited tumor growth and prolonged survival in preclinical models.

Conclusions:

  • Oncolytic vvDD demonstrates activity against treatment-resistant pediatric malignancies.
  • vvDD virotherapy warrants further investigation for refractory pediatric solid tumors.
Keywords:
Atypical teratoid rhabdoid tumors (AT/RT)Double-deleted vaccinia virusNeuroblastomaOncolytic virusPediatric tumorsSarcoma

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