A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer
| Autor: | Mary Harvey, Stephen J. Russell, Cory Allen, Cari J. McDonald, Charles Erlichman, Gabriela A. Rosales, Evanthia Galanis, James N. Ingle, Paula J. Zollman, Suzanne Greiner |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Paramyxoviridae Measles Vaccine Mice Nude Apoptosis Breast Neoplasms Virus Replication Virus Membrane Cofactor Protein Measles virus Mice Breast cancer Carcinoembryonic antigen Cytopathogenic Effect Viral Morbillivirus Chlorocebus aethiops Tumor Cells Cultured Animals Humans Medicine Mononegavirales Vero Cells Oncolytic Virotherapy Ovarian Neoplasms Mice Inbred BALB C biology business.industry biology.organism_classification medicine.disease Xenograft Model Antitumor Assays Virology Carcinoembryonic Antigen Oncolytic virus Survival Rate Oncology biology.protein Female business |
| Zdroj: | Breast Cancer Research and Treatment. 99:177-184 |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-006-9200-5 |
| Popis: | 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 x 10(7) 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink