Progress in cancer gene therapy

6 September 2006

A recent publication has revealed encouraging results for the use of gene therapy as a treatment for cancer [Morgan RA et al. (2006) Science Aug 31; Epub ahead of print]. Researchers from the US National Cancer Institute have used a retrovirus vector to introduce receptors into T-lymphocytes taken from seventeen patients with advanced metastatic melanoma, an aggressive form of skin cancer associated with very poor survival; the life expectancy of the patients at the time of treatment was reportedly 3-6 months (see BBC news report). The modified T-cells carried surface receptors designed to recognise and bind to the cancer cells via a surface molecule called MART-1, thereby enhancing immune destruction of these cells by the body. They were re-introduced into the patients and showed good persistence, or engraftment in fifteen patients; the tumour-specific T-cells comprised at least 10% of the total lymphocyte blood content for at least two months after treatment. In two of the seventeen patients, the modified anti-tumour cells showed long-term persistence in excess of one year, and in these patients the treatment led to total regression of the cancers. They have remained cancer-free for 18 months.

Experts agree that considerable improvements to the process will be required to make it suitable for greater numbers of patients and cancers the treatment failed to cure the majority of subjects in the trial - but the authors correctly observe that their results suggest the therapeuticpotential of genetically engineered cells as a treatment for cancer. Research team leader Dr Steven Rosenberg said that they would be seeking ways to enhance survival and persistence of the modified, tumour-specific T-cells, and also noted that they had successfully expressed lymphocyte receptors that specifically recognise multiple other forms of cancer, including breast and lung tumours. Of note, the therapy was not associated with any significant toxicity or side-effects, in contrast with aggressive forms of chemotherapy.

Although as with many gene-therapy approaches, considerable barriers will need to be overcome to make the technique more reliable and widely applicable - achieving long-term expression of therapeutic genes is a particular problem - these results are nevertheless a heartening 'proof-of-principle' demonstration of the potential power of gene therapy to combat cancers.

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