Scientists create tumour zapping T cells which knock out cancer

Aug 31 2006

Scientists in the United States have genetically engineered normal immune cells to become specialized fighters and used them to attack cancerous tumours.

Researchers at the National Cancer Institute (NCI) have demonstrated for the first time that such engineered cells can persist in the body and shrink large tumours in humans.

Of 17 people with advanced melanoma, a deadly form of skin cancer, who received the experimental treatment, two saw their tumours shrink and were declared clinically free of disease more than a year and half after the therapy began.

Steven A. Rosenberg of the National Cancer Institute and his team say the work represents the first time that gene manipulations have been shown to cause tumour regression in humans, and has demonstrated ways to engineer similar immune cells in the laboratory that would attack more common tumours such as breast, lung and liver cancers.

However fifteen patients failed to respond to the treatment and they say more work is needed to make it more effective.

The researchers removed tumour-fighting T cells from melanoma patients and multiplied these cells in the laboratory.

Chemotherapy was then used to clear out the patient's old T cells and the researchers re-populated the patients' immune systems with the new fighter cells.

Rosenberg says as some people with melanoma lack the tumour-fighting T cells, they had to come up with a way to create these types of T cells from scratch.

T cells carry a receptor protein on their surface that recognizes specific molecules called antigens on tumour cells and some cells contain genes that make a T cell receptor that targets melanoma cells, while other cells contain genes that make a T cell receptor that targets breast or lung cancer cells.

By removing normal T cells from people with melanoma, the researchers were able to genetically engineer them and create tumour fighters which were then returned to the body to rebuild the patients' immune systems.

The newly armed T cells showed signs of persistence in 15 of the patients in the study, making up at least 10 percent of their circulating T cells for at least two months after treatment but levels were higher in the two people whose tumours shrunk noticeably with the treatment.

Dr. Rosenberg, a senior surgeon at the NCI, says before the experiment, the patients had advanced skin cancer and standard therapies had failed; they were not expected to live longer than six months.

Rosenberg says over a year and a half later, the tumours have disappeared and both of the patients are now completely disease-free.

Rosenberg and his colleagues are now searching for ways to fine-tune the treatment so that greater numbers of the engineered T cells will survive and continue to express their new receptor genes.

Many scientists have long been vociferous advocates of gene therapy saying it promises cures for a range of diseases, but previous research has been fraught with controversy and safety concerns.

Rosenberg said there were no side effects from the melanoma gene therapy which was given with the drug interleukin-2.