Using our body’s immune system to fight cancer

When Science magazine named immunotherapy as the biggest research breakthrough of 2013, the editors themselves acknowledged “we are still at the beginning of this story and have a long way to go.” Just three years later, an increasing number of cancers can be controlled or cured by the body’s own immune system.

In Norway, immunotherapy has been approved and is being used to treat melanoma, and is approved to treat several of the most common types of lung cancers.

New forms of immunotherapy are also showing very promising results, with Norwegian researchers at the forefront of at least one development.

But how does immunotherapy actually work, and what are its benefits?

Harnessing the immune system

“There are different kinds of immunotherapy, but all work by getting the patient's own immune system to attack the cancer,” says Johanna Olweus, a researcher and professor at the University of Oslo and the Norwegian Radium Hospital who is also head of the K.G. Jebsen Centre for Cancer Immunotherapy. She spoke at a seminar organized in late November by the Norwegian Biotechnology Advisory Board.

Immunotherapy works for melanoma, renal cancer, lymphoma, leukaemia and certain types of lung cancer. It has a limited effect on other cancers, such as colon cancer.

The key to understanding immunotherapy lies in understanding the body's own immune system. In short, the body needs to recognize something as both foreign and dangerous before the immune system will react.

For example, when we get the flu, the body perceives the cells infected with flu virus as foreign. The inflammation caused by the virus, which results in flu symptoms such as fever and swollen lymph glands, is a danger signal that activates immune cells.

“But when we get cancer, the immune system unfortunately does not react,” Olweus said.

Pacified by cancer

Olweus says cancer cells can either kill immune cells outright or can cause them to become passive.

“A cancer patient’s immune cells may not react to damaged DNA or mutations in cancer cells,” she explained.

One reason for this is that the patient’s immune cells have evolved in lock step with the cancer cells over time.

“We have seen that a patient’s immune cells may only detect 2-5 of the 400 gene mutations in the average melanoma,” she says, which means they don’t see the cancer cells as foreign.

Cancer cells can also “turn off” a patient's immune cells to prevent them from going on the attack.

Immunotherapy works by giving the immune system outside help to recognize and attack cancer cells, or by blocking the ability of cancer cells to inhibit the immune system.

Checkpoint inhibitors

One form of immunotherapy is called checkpoint inhibition, which inhibits the interaction between immune cells and cancer cells that causes immune cells to be turned off. When this interaction is blocked, the immune cells can attack the cancer cells.

This development has brought hope to cancer patients for whom there was previously no hope at all.

Checkpoint inhibitors have been used successfully in malignant melanoma, kidney cancer, a specific type of lymphoma and some of the most common forms of lung cancer.

These cancers essentially have the most DNA damage of any cancers, which gives checkpoint inhibitors the best opportunity to stimulate immune cells to react. In spite of its successes, it works only for about 20-40 per cent of patients.

Stem Cell Therapy

Stem cell therapy, also called bone marrow transplantation, is also a form of immunotherapy. E. Donnall Thomas was awarded the Nobel Prize in Physiology or Medicine in 1990 for having developed this method.

“In this case, it is the (bone marrow) donor's immune cells that attack the cancer. This is a treatment that works for leukaemia and certain forms of lymphoma,” said Olweus.

The treatment is not without its risks, however.

Immune cells can also attack healthy cells in the patient's body, because the immune cells fail to differentiate between healthy and harmful cells, Olweus says. At worst, the patient may die.

Heat-seeking missiles

Researchers have also developed what are called CARS (Chimeric Antigen Receptors). CARS are "monster molecules" in which an antibody is combined with an immune cell receptor that can be activated.

“You can compare this to giving the patient's immune cells a heat-seeking missile for finding cancer cells. We harvest immune cells from the patient and modify them with genes that originated in mice,” says the Olweus.

Therapists often use viruses to introduce genes into cells. When the antibody part of a CAR molecule binds to its target on tumour cells, the genetically modified immune cells are activated and "detonated". 

This kills the cancer cells. Currently, the treatment can only be used for lymphoma and leukaemia.

Olweus and her colleagues have also published findings on a different kind of immunotherapy that relies on immune cells from donors to recognize cancer cell mutations in patients. The immune response from the donor cells can be introduced to patient’s immune system, allowing it to recognize and attack cancer cells. These results were published in Science magazine in May.

Fewer Side Effects

Immunotherapy often has fewer serious side effects than traditional treatments such as radiation therapy and chemotherapy, which can have serious side effects.

“Immune cells are weapons that spread around the body and can find cancer cells anywhere that they may be hiding,” Olweus said.

However, because the therapy stimulates an immune reaction, it can cause side effects in which the body attacks itself. Most of these side effects are manageable with medication.

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Read the Norwegian version of this article at forskning.no