University of Aarhus 2003
War in the body
The white blood cells wage war against cancer, and Doctor Marianne Hokland is their commander.
By Mikkel Hvid
“When it’s a success? That’s hard to say.”
Doctor Marianne Hokland pauses to think over the question.
“I haven’t really thought about what it would take before I could call the project a success,” she continues, “but I would be happy and proud if our project contributes to improving survival chances for future cancer patients. No. No, let me rephrase that. If our project can help increase the number of cancer patients who survive or get a better quality of life. Yes, that would really make me happy.”
Doctor Hokland conducts research into immune therapy. Her goal is to find and improve the parts of the body’s natural immune system that are best suited to fighting cancer.
The 52-year-old doctor has been interested in this subject since the mid-1970s, when she worked as a student assistant to Associate Professor Iver Heron at the Department of Medical Microbiology and Immunology. His work included using interferon, a substance that inhibits viral infections and that has also turned out to assist the body’s fight against certain types of cancer.
This project was a turning point in Doctor Hokland’s career. After a period at Harvard Medical School, she wrote her doctoral dissertation on a subject that went right back to her initial student project: how does interferon affect the cells in the immune system, and how can this effect be used as part of treatment based on the immune system? How do you strengthen and use the immune system so it can play a part in treatment?
The body versus cancer
During the past fifteen years, Doctor Hokland has focused on immune therapy in connection with skin cancer (malignant melanoma) and kidney cancer.
“The point is,” she says, “that the body has a natural, but very complex immune defence system against these conditions.”
Two elements are particularly important in this context: NK cells and T cells.
NK stands for natural killers, which are the body’s first line of defence.
The NK cells do not need to come into contact with the cancer before they realise that it is dangerous. They are, in fact, controlled by a “not me” principle, attacking whatever does not resemble themselves – and thus the body.
However, the NK cells present two problems. Firstly, they are not particularly effective, and secondly, they have difficulty identifying certain forms of cancer.
“Cancer cells form within us, so they resemble us,” explains Doctor Hokland. “The NK cells therefore have difficulty identifying them as hostile. They are too much like us.”
It is therefore fortunate that the body also has another line of defence, the T cells.
Once an enemy, always an enemy
The T cells are the body’s elite soldiers. They fight cancer much more effectively, but are unfortunately a bit slow off the mark. They have to come into contact with the cancer at least once to know that it is an enemy.
“The T cells have a memory. Once they have fought against a specific type of cancer, they know they must attack it next time they encounter it. So they attack very swiftly and effectively the second time round. That’s the principle used in vaccination programmes. Tetanus is a good example. You vaccinate the body with a little bit of tetanus to teach the T cells to recognise the organism. If the patient is later infected, the T cells act swiftly and effectively, because now they know exactly what to do.”
Once the T cells recognise a specific antigen, they go straight for the kill, and that is the basis of Doctor Hokland’s project. By using techniques such as flow cytometry, she is trying to find out what characterises the T cells that attack specific forms of cancer, so they can be used in cancer treatment.
“We’ve identified T cells that attack certain forms of cancer, but we do not have enough cells, and they are not effective enough. The main question driving my research at the moment is therefore to find out exactly what cell types we are talking about. Can we develop more? Can we make them more effective? That’s what I’m working on.”
Cells die when they are mass-produced
Doctor Hokland and her team of researchers are using a specific group of T cells to fight skin cancer and kidney cancer. These T cells identify the cancer and fight it. The only problem is that she loses too many of her soldiers in the heat of the battle.
“Far too many of the T cells we have found do not reach the cancer, and we haven’t yet managed to find out how the cells that do reach the tumour differ from those that don’t. And until we can answer that question, the treatment will not be good enough.”
Another problem facing Doctor Hokland is the difficulty associated with producing sufficient numbers of T cells. Normally, researchers remove cells from a blood sample and get them to divide in a test tube. However, doing this with the T cells that fight cancer is not always so easy.
“We can find and isolate the cells, but only in small quantities. We therefore have to activate them to get them to divide, but in doing so, we run the risk of them getting tired. In some cases, they actually commit suicide.”
This is a natural reaction. T cells were never meant to proliferate in uncontrolled numbers. If they did so, they would kill us.
“T cells are meant to go on developing as long as the disease is present and to die when it’s gone. But that makes it difficult for us to get hold of large numbers of them. It’s actually very difficult to imitate the body’s natural functions in a test tube.”
Immune therapy only kills the enemy
Instead of making use of the inherent “licence to kill” feature of the T cells, Doctor Hokland is conducting trials in another direction. She also uses them as carriers and suicide bombers.
Once the T cells that fight skin cancer, for example, have been identified, they can be used to transport lethal substances to the cancer.
However, Doctor Hokland is also encountering problems in this area. She cannot get enough T cells. And far too many of them do not reach their target.
She has nevertheless managed to get enough T cells to the cancer to allow visualisation on a PET scanner. This principle can be used to trace cancer that would otherwise be difficult to find.
And one day, she will succeed in using the T cells to fight cancer. She is certain of that. One day, they will find the type of T cell that is certain to reach the cancer, and they will also find out how to produce it. When that day comes, Doctor Hokland believes her research will have a decisive impact on practical cancer treatment, but it is unlikely to be the only form of treatment.
“I don’t believe in monotherapy. Combined forms of treatment are the thing of the future. But our therapy will contribute to future cancer treatment, and it has one major advantage. Our treatment attacks the cancer itself and nothing else, whereas chemotherapy and radiotherapy also affect other parts of normal cells. We hit the target, and only the target,” says Doctor Hokland.
| The Bartholin Building is named after the Danish anatomist Thomas Bartholin (1616-80), who first described the link between glands and the lymphatic system in humans. |
