Antitumour gene therapy - velimogene aliplasmid lipid complex

Replacing defective genes with ones that function properly sounds like a ideal way of curing diseases with a genetic basis such as hereditary conditions and cancer.

However, it's not as simple as that - not least because of the great difficulty involved in delivering the genes safely to the right place in the body, and then to integrate them with the body's own DNA. Many techniques that are being investigated involve viruses; others use nonviral vectors.

An example of the latter is velimogene aliplasmid lipid complex, or Allovectin-7, being developed by Vical.¹ The DNA plasmid gene transfer product combines the human leukocyte antigen HLA-B7, which has been cloned from a human B-cell library, and combined with chimpanzee ÃŽ²2 microglobulin. It is now being evaluated as a potential treatment for cancer, and is showing particular promise in malignant melanoma.

Numerous trials have already been carried out. For example, it was given to 17 HLA-B7 negative patients with metastatic melanoma.² They were given injections of 10-250µg of Allovectin-7 into their lesions, and half of them showed a reduction in the size of the injected nodules of at least a quarter, and one of them achieved a complete response. Biopsies of the tumours showed that two-thirds had detectable plasmid DNA.

In a Phase II trial, 52 patients with metastatic melanoma were given weekly injections for four weeks, and if there was no disease progression, two further doses were given.³ Nine had an overall tumour response, and two a systemic partial response, as well as several partial responses being seen.

Much higher doses have also been investigated: doses of 2mg were injected into 127 patients every week for six weeks.⁴ Fifteen patients had an objective response, and the median duration of this response was just over a year. There was no increase in toxicity with the higher dose. Trials continue, including comparison studies with standard chemotherapy regimes.