When a person develops cancer, the body’s immune defence is activated to destroy the tumour cells. By removing the most effective defence cells from the body, multiplying them and then returning them to the patient, scientists can help the body to fight the cancer itself. This immunotherapy is now being tested on several different types of cancer.

Immunotherapy is about giving the body’s own defences a head-start. When a tumour develops, the immune system normally starts to try to fight the cancer. But it does not always succeed, as tumour cells have various ways of getting round the body’s defences. For several years scientists at Karolinska Institutet have been working on a way of helping the bodys defence cells - lymphocytes - to beat the tumour.

Tumours spread through the body when tumour cells become detached and travel through the lymph vessels to the lymph nodes. The new method is based on identifying the “sentinel node” - the first lymph node draining the tumour. Virtually all of the bodys various types of lymphocytes will be found here. These kill invaders such as viruses and bacteria, and can also destroy tumour cells. In this way they protect the rest of the body against the spread of the tumour by fighting tumour cells arriving through the lymphatic fluid. The cells on which the scientists at Karolinska Institutet have been focusing are known as CD4 cells.

“CD4 cells stay in the body and remember a tumour for the rest of our lives, even after treatment is finished and the tumour has disappeared,” explains researcher and surgeon Magnus Thörn. “They act as a vaccine against that particular type of tumour.”

To get hold of the cells which are active against a tumour, the sentinel node where they will be found needs to be identified. This is done by injecting a blue dye around the tumour, which then spreads through the lymph. The first lymph node is soon revealed because it turns blue. The scientists can then remove the CD4 cells from the sentinel node and identify the ones which are active against the tumour. These cells are cultured in the laboratory together with parts of the tumour and other substances from the body to stimulate them to divide and multiply. Some 400-500 million cells can be grown over the next 28 days and then returned to the patient through a blood transfusion. This method - known as the SentoClone method - has managed to increase the survival of patients with metastatic colon cancer by more than 18 months relative to the standard treatment.

“We’ve been able to reduce or even eliminate tumours in these patients, both solid tumours and metastases where the cancer has spread,” says Thörn. “As the cells come from the patients themselves, we haven’t seen any side-effects, which can be very severe with other forms of cancer treatment.”

Together with Ola Winqvist, associate professor of clinical immunology at Karolinska Institutet, Thörn has also started up a company, SentoClone AB, to develop the method. The results to date come from a small unpublished study. The next step is a larger study of 80 patients with colon cancer at ten different hospitals, as well as smaller studies of malignant melanoma, bladder cancer and ovarian cancer.

If the sentinel node is free from tumour cells, this is a sign that the cancer has not yet spread. However, if it does contain cells from the tumour, this means that metastases may have taken place and that the cancer is also to be found in other parts of the body, Magnus Thörn explains. This led him to ponder the reasons why a tumour does or does not spread.

“Our hypothesis is that it’s not the tumour’s aggressiveness which determines whether it spreads in the body, but the properties of the lymphocytes which fight the tumour,” he says. “We know that the lymphocytes in patients with metastatic cancer have reduced activity. It has also been shown that patients with lots of CD4 cells in the tumour live longer.”

Recently the researchers reported that they had been able to find similar defence cells in the lymph nodes of patients with ulcerative colitis. These patients sometimes develop the early stages of cancer and run an increased risk of bowel tumours. The researchers hope that immunotherapy may also be useful in reducing the risk of future cancer in these patients.

Text: Cecilia Odlind, published in Medical Science, English edition 2007
Karolinska Institutet SE-171 77 Stockholm, Sweden