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.