The oncolytic properties of two newcastle disease virus strains
Abstract
English: Since the 1950's, several virus strains have been found to specifically infect and lyse human
carcinoma cells, while not causing serious side effects in the patient. However, the available
technology did not allow either sufficient characterization of, or research on these viruses
until the development of molecular biology technology. We are now able to further explore
this subject with renewed hope of "curing" cancer.
Newcastle Disease Virus (NOV) is a commonly occurring avian virus that is known not to
infect normal human cells or cause side effects other than mild conjunctivitis and laryngitis in
humans upon exposure to even the most virulent strains. Some NOV strains have been
shown to be oncolytic in recent studies. Much research remains to be done on the molecular
mechanisms, selectivity and biochemical apoptotic pathways involved in this oncolytic
mechanism.
Two of the most commonly occurring cancers in South Africa are cervical and esophageal
cancer.
The aim of this study was to assess the oncolytic properties of the two NOV strains La Sota
and Texas GB in vitro (in cell culture) and in vivo (in an immune compromized mouse
model).
In vitro results were promising: both strains were shown to be oncolytic, Texas GB more
aggressively than La Sota. Both strains were shown to induce apoptosis and polycaryocyte
formation, which leads to necrosis, in both cervical and esophageal cancer cell lines'.
In vivo, it was shown that intratumoural administration of either virus strain had either a
carcinostatic effect, or caused reduction in tumour volume in cervical cancer tumours in
immune compromized mice. In some cases the results were temporary and in other cases
the treatment had a prolonged effect. This is probably due to leakage of the inoculation from
the treatment site.
The results were not statistically significant due to the small number of mice used in the
study.
These results warrant further evaluation of the oncolytic efficiency of the La Sota strain of
NDV in immune competent mice, other cancer types and in clinical trials. Afrikaans: Sedert die 1950's is bewys dat sekere virusse menslike kankerselle infekteer en vernietig
sonder om ernstige newe-effekte in die pasiënt te veroorsaak. Die tegnologie was egter nie
van so 'n aard dat voldoende karakterisering van, of navorsing op hierdie virusse moontlik
was nie, tot die ontwikkeling van molêkulere biologie. Ons kan nou hierdie onderwerp verder
ondersoek met nuwe hoop vir die genesing van kanker.
Die Newcastle Siektevirus (NDV) is 'n algemene voëlvirus wat nie normale menslike selle
infekteer nie en ook geen newe-effekte behalwe matige konjunktivitis en laringitis in mense
veroorsaak nie, selfs nie met blootstelling aan die mees virulente stamme nie. Sommige
NDV stamme is onlangs bewys om onkolities te wees. Daar is egter nog baie navorsing
nodig om die molekulêre meganismes, selektiwiteit en biochemiese apoptose-weë wat
betrokke is in hierdie onkolitiese meganisme te ontrafel.
Twee van die algemeenste kankertipes in Suid Afrika is servikale en esofagus kankers.
Die doel van hierdie studie was om die onkolitiese eienskappe van die twee NDV stamme
La Sota en Texas GB te bepaal in vitro (in selkultuur) en in vivo (in 'n immuniteitsgebrekkige
muis model).
Die in vitro resultate was belowend: albei stamme was onkolities, hoewel Texas GB meer
aggressief was as La Sota. Albei stamme het apoptose en die vorming van polikariosiete,
wat lei tot nekrose, geïnduseer in beide die servikale en esofageale kankersellyne.
In vivo is bewys dat intratumorale toediening van enige van die twee virusstamme of 'n
karsinostatiese uitwerking het, of 'n afname in tumorvolume veroorsaak in servikale kanker
tumore in immuniteits-gebrekkige muise. In sommige gevalle was die resultate tydelik en in
ander gevalle van langer duur. Dit was waarskynlik na aanleiding van lekkasie van die
inokulum van die tumor. Die resultate was nie statisties betekenisvol nie as gevolg van die
klein getal muise wat in die studie gebruik is.
Hierdie resultate regverdig verdere evaluering van die onkolitiese effektiwiteit van die La
Sota stam van NDV in immuniteits-kompetente muise, ander kankertipes en in kiiniese
toetse.