Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.5.4.1 (
cytosine deaminase
)
747
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Therapy resistance and tumor recurrence are often linked to a small refractory and highly tumorigenic subpopulation of neoplastic cells, known as cancer stem cells (CSCs). A putative marker of CSCs is
CD133
(prominin-1). We have previously described a
CD133
-targeted oncolytic measles virus (MV-
CD133
) as a promising approach to specifically eliminate
CD133
-positive tumor cells. Selectivity was introduced at the level of cell entry by an engineered MV hemagglutinin (H). The H protein was blinded for its native receptors and displayed a
CD133
-specific single-chain antibody fragment (scFv) as targeting domain. Interestingly, MV-
CD133
was more active in killing
CD133
-positive tumors than the unmodified MV-NSe despite being highly selective for its target cells. To further enhance the antitumoral activity of MV-
CD133
, we here pursued arming technologies, receptor extension, and chimeras between MV-
CD133
and vesicular stomatitis virus (VSV). All newly generated viruses including VSV-
CD133
were highly selective in eliminating
CD133
-positive cells. MV-CD46/
CD133
killed in addition
CD133
-negative cells being positive for the MV receptors. In an orthotopic glioma model, MV-CD46/
CD133
and MV
SCD
-
CD133
, which encodes the super
cytosine deaminase
, were most effective. Notably, VSV-
CD133
caused fatal neurotoxicity in this tumor model. Use of
CD133
as receptor could be excluded as being causative. In a subcutaneous tumor model of hepatocellular cancer, VSV-
CD133
revealed the most potent oncolytic activity and also significantly prolonged survival of the mice when injected intravenously. Compared to MV-
CD133
, VSV-
CD133
infected a more than 10
4
-fold larger area of the tumor within the same time period. Our data not only suggest new concepts and approaches toward enhancing the oncolytic activity of
CD133
-targeted oncolytic viruses but also raise awareness about careful toxicity testing of novel virus types.
...
PMID:Enhancing the Oncolytic Activity of CD133-Targeted Measles Virus: Receptor Extension or Chimerism with Vesicular Stomatitis Virus Are Most Effective. 2869 8
