Dendritic cells help the body to switch on an immune response by seeking out foreign proteins (antigens) and showing them to the T and B cells. They are normally present all over the body but only in very small numbers, which means that they are difficult to isolate and study. At the British Society for Immunology Annual Congress in Brighton this week, Dr Jonathan Austyn of the University of Oxford will explain how recent advances have made it possible to grow large numbers of dendritic cells in the lab, opening the way to their use in the treatment of cancer.
Cancers may develop because the immune system is not given a strong enough signal to destroy the tumour. There is even evidence that, in some cases, cancers are able to turn off the immune response. For example, immature dendritic cells are found in some cancers. However, substances produced by the tumour prevent the cells from developing into a more mature form which can stimulate an immune response. These substances may even cause the death of the dendritic cells.
However, immunologists now think it should be possible to over-ride the effects of these substances. Dendritic cells can be separated from the patient's blood or bone marrow and grown in large quantities in culture. They can then be shown bits of the tumour to which the immune system will react (tumour antigens) and reinfused into the patient. A recent clinical trial using this approach in the United States was most encouraging.
In certain types of cancer, such as the skin cancer malignant melanoma, it is known that patients can mount an immune response to the developing tumour. However, in many cases this response ultimately fails. Could treating patients with beefed-up dendritic cells help to maintain this response?
Dr Austyn and his colleagues will be starting a Phase I clinical trial early in 1998 where they will use dendritic cells to try to treat patients with advanced (Stage IV) malignant melanoma or breast cancer. The patients in the trial have not responded to conventional treatments and have metastatic skin lesions.
Dendritic cells from the patients' blood will be grown and induced to develop into their mature form in culture. They will then be injected directly into the skin lesions. The team hope that the mature dendritic cells will pick up tumour antigens and switch on an immune response.
One problem that Dr Austyn foresees is that patients with advanced cancer often have weakened immune systems. Therefore it is possible that even the most potent dendritic cells will not be able to switch on a strong enough immune response to totally eradicate cancers. However, Dr Austyn suggests that this problem may be overcome by using dendritic cells in conjunction with other types of immunotherapy.
Dendritic cell therapy alone may also prove useful for patients at high risk of recurrence after a primary tumour has been removed by surgery, or for healthy people at risk of developing familial types of cancer.
Notes:
1. Dr Austyn is speaking in the Vaccines session on Thursday 4 December. The
BSI 5th Annual Congress is at the Brighton Centre, Brighton, UK from 2-5
December 1997
2. Dr Austyn can be contacted at the Nuffield Department of Surgery, University
of Oxford, The John Radcliffe Oxford Radcliffe Hospitals NHS Trust, Headington,
Oxford OX3 9DU. Tel: +44 1 865 221 281 Fax: +44 1 865 768 876
jon.austyn@surgery.oxford.ac.uk
3. There will be a press office at the meeting in operation from 9am on Tuesday
2 December. Tel: +44 1 273 724 320 / 0378 406 416. Journalists are welcome to
attend but are asked to contact Kirstie Urquhart in advance to register.
4. Before the meeting Kirstie can be contacted on +44 181 875 2402 /
kirstie@immunology.org