An oncolytic measles virus-sensitive Group 3 medulloblastoma model in immune-competent mice.
Neuro Oncol
; 20(12): 1606-1615, 2018 11 12.
Article
in En
| MEDLINE
| ID: mdl-29912438
ABSTRACT
Background:
Oncolytic measles virus (MV) is effective in xenograft models of many tumor types in immune-compromised mice. However, no murine cell line exists that is tumorigenic, grows in immune-competent mice, and is killed by MV. The lack of such a model prevents an examination of the effect of the immune system on MV oncotherapy.Methods:
Cerebellar stem cells from human CD46-transgenic immunocompetent mice were transduced to express Sendai virus C-protein, murine C-Myc, and Gfi1b proteins. The resultant cells were injected into the brain of NSG mice, and a cell line, called CSCG, was prepared from the resulting tumor.Results:
CSCG cells are highly proliferative, and express stem cell markers. These cells are permissive for replication of MV and are killed by the virus in a dose- and time-dependent manner. CSCG cells form aggressive tumors that morphologically resemble medulloblastoma when injected into the brains of immune-competent mice. On the molecular level, CSCG tumors overexpress natriuretic peptide receptor 3 and gamma-aminobutyric acid type A receptor alpha 5, markers of Group 3 medulloblastoma. A single intratumoral injection of MVâgreen fluorescent protein resulted in complete tumor regression and prolonged survival of animals compared with treatments with phosphate buffered saline (P = 0.0018) or heat-inactivated MV (P = 0.0027).Conclusions:
This immune-competent model provides the first platform to test therapeutic regimens of oncolytic MV for Group 3 medulloblastoma in the presence of anti-measles immunity. The strategy presented here can be used to make MV-sensitive murine models of any human tumor for which the driving mutations are known.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cerebellar Neoplasms
/
Disease Models, Animal
/
Oncolytic Virotherapy
/
Immunocompetence
/
Measles virus
/
Medulloblastoma
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Neuro Oncol
Journal subject:
NEOPLASIAS
/
NEUROLOGIA
Year:
2018
Document type:
Article