Can gene therapy substitute for surgery to remove a brain tumour? Clinical trials, involving 15 patients at the National Institute of Health in Bethesda, US point to a positive answer.

A team led by Michael Blaese claims concrete proof of gene therapy being a practical approach to tackle cancer. Blaese, chief of the Clinical Gener Therapy Branch of the National Centre for Human Genome Research at the NIH, has used ‘suicide genes’ from the herpes simplex virus riding into brain tumour cells on retroviruses have RNA and DNA as their genetic material, but need an intermediate DNA for replication.

The first trial was encouraging enough for us to continue with a large trial that addresses itself to patients suffering from high-grade brain cancer, people who do not have more than six months to live. His technique is based on exploiting a characteristic feature of the retroviruses – that they can transfer genes only into actively dividing cells. A cancerous cell or tumour divides prolifically whereas healthy brain cells do not divide at all. This means the retrovirus carrying the herpes simplex gene will enter only the abnormal brain cells.

As the brain is more immunologically privileged than those other parts of the body, it allows these incompatible cells from the mouse to persist without any rejection or reaction. Once the HS-tk gene gets into the cancer cells of the tumour, it makes those cells behave just like virus cells. Blaese says, “We have used HS-tk in order to change the metabolism of the tumour cell so that it would mimic the cell of a virus. Then we can treat the tumour cell with an anti-viral drug.”

After being treated with a retrovirus, patients are put on Ganciclovir. Ganciclovir, a common anti-herpes drug, kills the cancerous cells which appear like viral cells thanks to the HS-tk gene in them. This function of the HS-tk has earned it the name of a ‘suicide gene’.

Though the suicide genes are not put into each cancerous cell in the procedure, tumour regression is almost complete after gene therapy. This, according to Blaese, is the result of the ‘bystander effect’ that is, the poison produced by the gene can spread to adjacent cells of the tumour through gap junctions.

The first phase of the clinical trials was designed to test the efficiency of the method and to probe its possible toxic effects. From the target group of 15 patients, one survived for 25 months, increasing the expected life span of 19 months! I do not want to mislead people by saying this is the magic bullet that is going to cure brain cancer, but I do not hope this will be another tool that is effective in cancer treatment.

What if the virus spreads to non-tumour tissues within or outside the central nervous system? What if the viral cells proliferate right where they are injected? And there is the possibility of the interaction between the Hs-tk and Ganciclovir this generating toxic by-products that might damage even healthy cells.