A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer

Cari J. McDonald, Charles Erlichman, James N. Ingle, Gabriela A. Rosales, Cory Allen, Suzanne M. Greiner, Mary E. Harvey, Paula J. Zollman, Stephen J Russell, Evanthia Galanis

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Breast cancer is the most common malignancy and the second leading cause of female cancer mortality in the United States. There is an urgent need for development of novel therapeutic approaches. In this study, we investigated the antitumor potential of a novel viral agent, an attenuated strain of measles virus deriving from the Edmonston vaccine lineage, genetically engineered to produce carcinoembryonic antigen (CEA) against breast cancer. CEA production as the virus replicates can serve as a marker of viral gene expression. Infection of a variety of breast cancer cell lines including MDA-MB-231, MCF7 and SkBr3 at different multiplicities of infection (MOIs) from 0.1 to 10 resulted in significant cytopathic effect consisting of extensive syncytia formation and massive cell death at 72-96 h from infection. All breast cancer lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production. TUNEL assays indicated an apoptotic mechanism of syncytial death. The efficacy of this approach in vivo was examined in a subcutaneous Balb C/nude mouse model of MDA-MB-231 cells. Intravenous administration of MV-CEA at a total dose of 1.2×107 TCID50 resulted in statistically significant tumor growth delay (p=0.005) and prolongation of survival (p=0.001). In summary, MV-CEA has potent antitumor activity against breast cancer lines and xenografts. Monitoring marker peptide levels in the serum could serve as a low-risk method of detecting viral gene expression during treatment and could allow dose optimization and individualization of treatment. Trackable measles virus derivatives merit further exploration in breast cancer treatment.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalBreast Cancer Research and Treatment
Volume99
Issue number2
DOIs
StatePublished - Sep 2006

Fingerprint

Measles Vaccine
Measles virus
Carcinoembryonic Antigen
Breast Neoplasms
Viral Genes
Infection
Virus Receptors
Gene Expression
Second Primary Neoplasms
In Situ Nick-End Labeling
Giant Cells
Therapeutics
Heterografts
Nude Mice
Intravenous Administration
Neoplasms
Cell Death
Vaccines
Viruses
Cell Line

Keywords

  • Breast cancer
  • CEA
  • Measles virus
  • MV-CEA
  • Virotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer. / McDonald, Cari J.; Erlichman, Charles; Ingle, James N.; Rosales, Gabriela A.; Allen, Cory; Greiner, Suzanne M.; Harvey, Mary E.; Zollman, Paula J.; Russell, Stephen J; Galanis, Evanthia.

In: Breast Cancer Research and Treatment, Vol. 99, No. 2, 09.2006, p. 177-184.

Research output: Contribution to journalArticle

McDonald, CJ, Erlichman, C, Ingle, JN, Rosales, GA, Allen, C, Greiner, SM, Harvey, ME, Zollman, PJ, Russell, SJ & Galanis, E 2006, 'A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer', Breast Cancer Research and Treatment, vol. 99, no. 2, pp. 177-184. https://doi.org/10.1007/s10549-006-9200-5
McDonald, Cari J. ; Erlichman, Charles ; Ingle, James N. ; Rosales, Gabriela A. ; Allen, Cory ; Greiner, Suzanne M. ; Harvey, Mary E. ; Zollman, Paula J. ; Russell, Stephen J ; Galanis, Evanthia. / A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer. In: Breast Cancer Research and Treatment. 2006 ; Vol. 99, No. 2. pp. 177-184.
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