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Cloned immune cells treat skin cancer

Thursday 19 June 2008

“A cancer patient has made a full recovery after being injected with billions of his own immune cells in the first case of its kind,” The Daily Telegraph reported today. The newspaper described how a 52-year-old man with advanced melanoma, a type of skin cancer that usually has a poor prognosis once it has spread, has made a full recovery. The story said that after two years he is still free from the disease, which had spread to his lymph nodes and one of his lungs.

This case report received a lot of press coverage, and most reports were careful to put the study into context. The researchers themselves avoid the word cure, since this type of cancer is notorious for re-occurring at a late stage, even after two years. Although this is a landmark in the treatment of metastatic melanoma, other cancer types in different body sites are expected to behave differently and the researchers do not assume the treatment will be helpful for all cancers.

It would be wise to wait for the reports of the full series of patients (as well as larger controlled trials) before fully evaluating the practicalities and possible downsides to this innovative treatment.

Where did the story come from?

Dr Naomi Hunder from the Fred Hutchinson Cancer Research Center, Seattle and colleagues from the University of Washington in Seattle and the Memorial Sloan-Kettering Cancer Center in New York carried out the research. The study was supported by grants from the National Institutes of Health, the General Clinical Research Center, the Edson Foundation and the Damon Runyon Cancer Research Foundation. The study was published as a brief report in the peer-reviewed New England Journal of Medicine.

What kind of scientific study was this?

Previous studies show that some T-cells - a special type of white blood cell involved in the immune response - can be used to treat people with metastatic melanoma. The subtypes of these cells known as CD4+ and CD8+ have an anti-cancer effect by interacting with each other and producing substances that directly or indirectly destroy tumour cells.

In this case report, the researchers described the results of an innovative treatment of metastatic melanoma in a 52-year-old patient. Metastatic melanoma is a type of skin cancer that spreads beyond the skin to other areas of the body, and is notoriously difficult to treat.

The patient in this case report had had a melanoma skin cancer removed but this had returned. He had also been unsuccessfully treated with several conventional chemotherapy treatments. At the last recurrence of his disease, he had deposits (metastases) in the lung and in the lymph nodes of the groin and pelvis. The researchers checked for further disease and recorded the precise location of the deposits by using magnetic resonance imaging (MRI-scan) of the brain and computed tomography (CT-scan) of the chest, abdomen, and pelvis. This confirmed the position and size of the deposits, and showed that he had not developed brain metastasis. He also had a positron-emission tomography (PET-scan) of his entire body, which showed that no other areas were affected.

Using a biopsy of the melanoma, the researchers identified a specific protein, (NY-ESO-1) found on the surface of the cells that could be used to identify the cancer. They then collected white blood cells from the patient’s blood and grew them in the presence of part of the NY-ESO-1 protein, which acted as an “antigen”, meaning that it provoked an immune response. The researchers then separated out only the T-cells that recognised and attacked the NY-ESO-1 protein. They then used novel techniques to generate a large number of identical CD4+ T-cells that would direct the immune system to attack the tumour cells that carried the NY-ESO-1 protein. Several billion of these cells were then injected back into the patient. Over the next three months his antibody response and the number of T-cells in his blood were monitored.

Two months after the treatment they also carried out PET and CT scans to look for any signs of the original metastases or to detect any new ones.

What were the results of the study?

For their results, the researchers describe the method they have developed that isolated a patient’s CD4+ T-cell and expands those specific to the melanoma-associated antigen NY-ESO-1.

The researchers report that PET and CT scans carried out two months after the cells were injected into the patient found no evidence of cancer and, after 22 months, there was still no sign of recurrence. The researchers last had contact with the patient 26 months after the injection and he had not needed any further cancer treatment and could function normally with no obvious symptoms of disease. The treatment also did not seem to induce any side effects related to the immune system.

In addition, they noted that the treatment also induced T-cells to respond to melanoma antigens other than NY-ESO-1.

What interpretations did the researchers draw from these results?

In their interpretation of this study, the researchers said they had showed that injecting “a clonal population of CD4+ T cells with specificity for a single tumour-associated antigen caused complete regression of a tumour”.

They also said that “during regression of the tumour, this clone appears to have induced the patient’s own T cells to respond to other antigens of his tumour.” This means that the cloned T-cells that recognised the NY-ESO-1 protein appeared to make the patient’s own T-cells respond to other proteins on the surface of the tumour.

What does the NHS Knowledge Service make of this study?

The results of the study, while encouraging, should be put into context. This study is a good illustration of the role of a single case report in identifying suitable areas for further research. The researchers are careful to avoid saying that they have found a cure for this stage and type of cancer. They do not speculate on the implications of their findings for other cancers beyond saying that “these findings support further clinical studies of antigen-specific CD4+ T cells in the treatment of malignant disease”.

This case report does not describe any results for other people that may have been offered the treatment. It does not clarify the extent of the clinical examination, nor which tests were performed at 22 months.

The newspapers mention nine other patients who received similar treatment. It would be wise to wait for the reports of this case series (as well as the results of larger controlled trials) before fully evaluating the practicalities and possible downsides to this treatment.

Sir Muir Gray adds...

Someone has to be the first to receive a new treatment, but had I been offered this treatment as part of a research project I would have accepted the offer. Research is a type of intervention which can be offered ethically when there is uncertainty about what to do next.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Clone cell cancer 'cure' hailed

BBC News, 19 June 2008

Clone science hope for skin cancer cure.

Daily Express, 19 June 2008

Cancer ‘cured’ with cell clones.

The Sun, 19 June 2008

Skin cancer patient 'cured' using his own blood cells.

The Independent, 19 June 2008

Cancer patient recovers after injection of immune cells.

The Daily Telegraph, 19 June 2008

Patient fights off cancer with clones of his own immune cells.

Daily Mail, 19 June 2008

Cloned immune cells cleared patient's cancer.

The Guardian, 19 June 2008

Links to the science

Hunder NH, Wallen H, Cao J, et al.

Treatment of Metastatic Melanoma with Autologous CD4+ T Cells against NY-ESO-1.

N Eng J Med 2008; 358:2698-2703