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The history of immunotherapy

A scientist working in a laboratoryIn the 1850s, doctors in Germany noticed that patients' tumours would occasionally shrink if their tumour became infected. This observation led to the idea that the body's immune system could be harnessed and made to fight cancer.

Around the same time, doctors throughout Europe, encouraged by the success of Edward Jenner's smallpox vaccine, attempted to make a 'cancer vaccine' by injecting patients with crude extracts of tumours from other cancer patients. These treatments were largely ineffective, but the field of 'immunotherapy' was born.

Initial progress on immunotherapy was slow, and over a hundred years' work in the laboratory yielded little success in actual cancer treatment. This all changed when in 1975, Georges Köhler and César Milstein, working in Cambridge, discovered how to make synthetic antibodies.

Their discovery, coupled with an ever-increasing understanding of the immune system, has led to a variety of treatments and strategies that use the immune system to tackle cancer. Some, such as the antibody-based breast cancer drug Herceptin, are now used routinely to treat cancer patients.

Immunotherapy can be local or systemic.

Local immunotherapy delivers the treatment to the affected area. For example, the BCG vaccine can be injected into the bladder to treat bladder cancer, as it causes inflammation that can cause the tumour to shrink.

Systemic therapy treats the whole body and is useful for targeting cancer that may have spread. In the 1980s, scientists at the Cancer Research UK Medical Oncology Unit at the Christie Hospital in Manchester showed that the protein interferon alpha could cause tumours to shrink in patients with low-grade lymphoma. Interferon is now used to treat several different types of cancer.

Immunotherapy can also be non-specific or targeted.

Non-specific immunotherapy works by boosting the body's immune system in general, so that its natural cancer-killing activity is enhanced. Both of the examples of local and systemic therapies (above) are also examples of non-specific immunotherapy.

Targeted immunotherapy is designed to make the immune system specifically kill cancer cells. The following types of targeted immunotherapy are available or are in development:

Antibody-based therapies

Antibodies are proteins produced by the immune system. A type of white blood cell called a B-cell produces them in response to an infection. Normally, antibodies stick to foreign objects in the body and label them for destruction. Researchers have been trying to make antibodies that will attach themselves only to cancer cells. This can be useful in four ways.

  • It can stop the cancer from growing by stopping other essential 'growth factors' from sticking to it.
  • It can 'tag' the cancer for destruction by the immune system.
  • If cancer drugs or radioactive particles are attached to the antibody, it can deliver them directly to the cancer cell without harming the rest of your body.
  • An enzyme (a type of protein that can promote chemical reactions) can be attached to an antibody, and then given to a patient along with a chemical that can be turned into a powerful drug by the enzyme. This directs the drug to the cancer, and minimise side effects. This process is known as Antibody-directed Enzyme/Pro-drug Therapy (ADEPT).

Several antibody-based therapies are available, including the breast cancer drug Herceptin.

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