Anticancer agent - JX-594
Another way of treating cancer is by stimulating the immune system with a targeted oncolytic virus. But this has limitations, as although the viruses can inhibit tumour growth, they have not been able to eradicate distant metastases.
Another way of treating cancer is by stimulating the immune system with a targeted oncolytic virus. But this has limitations, as although the viruses can inhibit tumour growth, they have not been able to eradicate distant metastases.
Jennerex Biotherapeutics has developed a targeted vaccinia virus by inserting granulocyte-macrophave colony stimulating factor (GM-CSF) and β-galactosidase genes into the virus, which inactivates the thymidine kinase gene.1 This decreases the virulence of the virus, and also increases its ability to kill cancer cells with cell cycle abnormalities and epidermal growth factor/Ras pathway activation. It is able to replicate within tumour cells, releasing tumour antigens, and direct oncolysis and GM-CSF expression stimulates the shutdown of tumour vasculature and antitumoral immunity.
In a non-comparative open label Phase I dose escalation trial, 14 heavily pretreated patients with refractory primary or metastatic liver tumours were given one of four doses of intratumoral JX-594 - 1x108, 3x108, 109 or 3x109 plaque forming units, every three weeks.2 All patients experienced grade 1-3 flu like symptoms, and four had transient dose related thrombocytopenia. Dose limiting hyperbilirubinaemia was observed in both patients at the highest dose, so the maximum tolerated dose was set at 1x109 PFU. Of the 10 patients who could be evaluated by radiography for an objective response, three had a partial response to the treatment, six had stable disease and one had progressive disease.
It has also been investigated in three patients with advanced refractory hepatitis B virus associated hepatic cell carcinoma.3 Subjects were given the virus by intratumoral administration, and it was well tolerated, giving an antitumour effect in all three patients, even though high levels of neutralising antibodies were present. It induced antivascular cytokines, and was associated with tumour vascular shutdown, and also suppressed underlying hepatitis B virus replication.
Phase II trials are now under way.