Blog Against Cancer

Immunotherapy: could it be the cure for cancer?

The body’s own defences could be the key to defeating the disease, reports Roger Highfield

It sounds like a hippy approach to medicine: everyone has the power within them to heal cancer and all we have to do is to find a way to unlock our inner potential.

Oncologist Dr. Steven Rosenberg holding up bag of lymphocytes in medium to check for growth of cancer killing T cells at the National Cancer Institute.
Oncologist Dr Steven Rosenberg holding up bag of lymphocytes to check for growth of cancer killing T cells

But an increasing number of studies are reaching exactly that conclusion when it comes to treating cancer with immunotherapy, in which the body’s protective cells are turned on a tumour. Or, put another way, patient, heal thyself.

A few weeks ago, it was revealed that a 52-year-old man was free of skin cancer, two years after being injected with his own cells - the most recent in a series of immunotherapy studies which have offered similar tantalising successes. And this week, a major journal will publish the latest studies, suggesting that this approach is on the right track.

The problem is that current conventional cancer treatments are crude. Surgery to cut out the cancer can work, if it has not spread elsewhere in the body. Or, given that rapidly dividing cancer cells are more vulnerable to damage than normal cells, another approach is to blitz them with toxins -chemotherapy drugs - or radiation.

There is also a new generation of treatments emerging, based on understanding how genetic changes in a cell make it run amok and create a tumour. But a recurring problem with any treatment is that cancer cells that are not killed tend to be mutant ones that can rapidly evolve to outwit these smart drugs.
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In comparison, immunotherapy revolves around bolstering the body’s own defences so that they can mount an effective attack on cancer. One of the pioneers in this field is Dr Steven Rosenberg, now at the National Institutes of Health, Bethesda.

He was inspired by witnessing a spectacular, and extremely rare, case of a spontaneous remission from cancer - in 1969, he came across a patient who wanted a gall bladder removed. But when Rosenberg checked his records, he found that the patient had been sent home to die more than a decade earlier with stomach cancer.

Rosenberg then began a long series of tests on animals, and the important discovery that the patient’s own white blood cells must first be depleted to give immunotherapy a chance to work (originally, Rosenberg found that the majority of transferred cells did not survive, but that by suppressing the patients’ immune systems to “make room” for the new cells, as doctors do during a tissue transplant, he could make the transferred cells survive, grow in the body and begin killing the tumour cells).

Finally, in 1994, after infusing a patient’s white blood cells which had been selected for their anti-tumour activity (called T cells), he reported success using the cells to fight melanoma, the deadly form of skin cancer.

Two years ago, he announced striking results after using the first gene-engineered cells. This time the patient’s T cells had undergone a gene transplant to make them attack tumours. Of the 17 patients who took part, the results were stunning for Mark Origer, who was suffering from an advanced form of the disease, so-called metastatic melanoma that had spread to seed daughter tumours throughout the body.

The trial started in 2004. In December that year, Origer had white blood cells removed and genetically altered with the help of a virus (viruses are commonly used to introduce genes, in this case to make the white blood cells more effective cancer fighters). After five years of losing the battle with the disease, Origer was well enough to attend his daughter’s wedding in September of 2005.

What is so remarkable is that the cancer had spread to Origer’s liver, where it is usually extremely hard to treat. Yet, by the time of the wedding, only one small spot remained in his liver, which surgeons removed. Another patient, “Thomas M”, also staged a remarkable recovery -but the other 15 did not respond to the treatment.

“We have now treated 93 patients with metastatic melanoma using their own anti-tumour cells with a response rate (slowing of disease, or shrinking of tumours) of 72 per cent - about three times better than any other treatment,” said Dr Rosenberg, who is now using the approach of what he calls “adoptive cell transfer” to deal with other cancers, such as prostate, endometrial and kidney cancers.

A few weeks ago, a simpler kind of immunotherapy was announced by Dr Cassian Yee, who led a team at the Fred Hutchinson Cancer Research Centre in Seattle. Once again, he focused on melanoma and used hand-picked white blood cells to combat the cancer.

The researchers isolated a handful of these cells from patients whose melanoma had spread. All the cells recognised a protein called NY-ESO-1 - which existed in the tumour, but not most healthy cells. When injected back into the body, the lab-grown cells started to attack this and other tumour molecules.

he most dramatic results in this preliminary trial were seen, as mentioned above, in a 52-year-old man, who was suffering from advanced skin cancer that had spread to his lymph nodes and one lung. Within eight weeks of undergoing the procedure, when five billion of his own immune cells were injected, he was free from tumours. Two years on, he remains clear of the disease.

Yet there is still a need for large-scale trials to understand why the outcome of immunotherapy is so spotty: it can have no effect on some patients, and dramatic ones on others. In the Seattle trial, the patient who was cleared was one of nine with metastatic melanoma. The other eight did not do as well. Another problem is that it is a major exercise to grow a patient’s own cells in the lab - it costs tens of thousands of dollars per patient, said Dr Yee.

Now there is an alternative. The company Micromet, which has its headquarters in Bethesda, Maryland, and does its research in Munich, Germany, is developing an elegant way to recruit anti-cancer cells, in the bodies of the patients themselves. Christian Itin, the CEO of Micromet, said they were using antibodies, called BiTE antibodies, which are able to activate T cells to attack cancer.

One problem with immunotherapy, he explained, is that as tumours become more advanced they become more “invisible” to the white blood cells because the cancer cells lack molecules for white blood cells to hang on to and stage their attack. Normal antibodies are designed to latch on to one molecular target but those developed by Micromet bind to two, the cancer cell and the T cell, and bring the two together. “They instruct the T cells to attack and kill the tumour cells,” said Itin.

Phase one and two clinical trials of the BiTE antibodies are now underway in Europe, including patients with lung and gastrointestinal cancer. Recently, at the International Conference of Malignant Lymphomas, the company presented an update on their trial for MT103, the BiTE antibody being tested for a cancer of the lymphatic system, non-Hodgkin’s lymphoma.

All seven patients enrolled so far (all of whom had exhausted conventional treatments) have had either a complete or partial response. This included some whose cancer had spread to the bone marrow. Remissions for all these patients continue, with the longest being for more than a year.

According to Prof Michael Keating, at the University of Texas MD Anderson Cancer Centre, this kind of immunotherapy shows promise when it comes to blood cancers. Meanwhile, other BiTE therapies - for cancers including melanoma, lung and gastrointestinal cancer - are in development.

Although there have been many false dawns in the worldwide effort to improve cancer treatments experts believe that the latest studies could represent a landmark.

Source: www.telegraph.co.uk