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Vaccine therapy and cancer

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VOL: 96, ISSUE: 47, PAGE NO: 36

Annie Angle, RN, is senior cancer information nurse, Cancer Research Campaign

Annie Angle, RN, is senior cancer information nurse, Cancer Research Campaign

Rarely a month goes by without another news story on the latest wonder cancer vaccine. While this may be encouraging for many people, in fact vaccine therapy is still in its early stages and clear evidence of its benefits still needs to be provided.

No cancer vaccine has yet been developed to become a standard treatment and the results from trials so far show that only a small number of patients were able to benefit from the vaccines.

What is happening, however, is that knowledge of the human genome is opening up new prospects for vaccines, both in terms of identifying target molecules and enhancing our understanding of the immune system.

Doctors are aware that they need to carry out more clinical trials and to work with scientists to perfect these new treatments (Crowley, 1999).

While existing treatments continue to be the first choice, if these have not been completely effective doctors may suggest their patients enter a vaccine therapy trial.

Theoretical background

To understand how cancer vaccines work, it is helpful to revise normal immune response mechanisms.

The immune system is our natural defence system against disease. When a germ or other 'foreign invader' enters the body, the immune system usually responds in force.

The body's immune system consists of a network of organs (spleen, lymph nodes and thymus) and specialised cells and tissues, such as the bone marrow.

The immune cells originate in the bone marrow and arise from a basic type of cell called a stem cell. Many different types of immune cells are produced from stem cells (see Fig 1).

The cells of the immune system circulate throughout the body in the blood or in the lymphatic system and are stored in lymph nodes, (for example, in the neck, abdomen, lungs or armpits). When a lymphocyte recognises its specific antigen, it is activated and the lymphocyte then reproduces many identical copies of itself, each recognising the same antigen. The immune system is programmed to respond only to things it sees as being 'foreign' or 'non-self'. These are called foreign antigens, a term used to describe substances not usually present in the body, such as invading organisms.

Foreign antigens can cause the immune system to react and destroy not just the antigen but also anything else attached to it, including cancer or bacterial cells (National Cancer Institute, 2000).

The discovery that cells become cancerous because they contain defects caused by genetic mutations was made about 20 years ago. Such changes can be detected by the immune system.

But the immune system is more efficient at recognising germs than cancer cells, because the differences between normal cells and cancer cells are quite small. Therefore, if the immune system does recognise the cancer cell antigens as foreign, it may not be able to react sufficiently to kill the cancer.

Various types of immunotherapies have been developed to enhance recognition of cancer-cell antigens as targets for attack, and to strengthen the attack so that it will destroy the cancer.

Historical background

The idea of cancer immunotherapy is not new. Scientific evidence to support the idea that the immune system might control the development of a cancer emerged in the 1800s. Physicians noticed some tumours regressed in patients who contracted a bacterial infection.

Professor B Coley, a surgeon in New York City from 1892 to 1936, dedicated his life to creating cancer therapies based on this observation. He deliberately infected some cancer patients and later devised a vaccine consisting of killed bacteria to prompt tumour regressions. But Coley's successes were not readily reproducible by others and his treatment proved controversial, leading to nearly two decades of delayed development (Dalgleish, 2000).

New insights have generated great interest in immunotherapy treatments for cancer. Means have been found of isolating the cells and chemicals that stimulate the immune system to attack foreign antigens (Baar, 1999).

Types of cancer vaccines

Because treating an established cancer is a difficult task, most cancer vaccines are used in combination with existing immunotherapy treatments that help stimulate the immune system in a general, rather than a specific, way. The substances used in these therapies are called cytokines or adjuvants.

There are three types of immunotherapy currently available or being investigated:

- Non-specific immunotherapies and adjuvants (cytokines such as interferons, interleukins, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), BCG)

- Passive immunotherapies (monoclonal antibodies produced in the laboratory rather than by the patient's own immune system. Very much like anti-snake bite therapy);

- Active, specific immunotherapies (cancer vaccines).

Sometimes doctors will use two or more of these immunotherapy options together.

Most of the cancer vaccines on trial are used to treat, rather than prevent cancer. They are given to a person who already has cancer to try to prompt the patient's immune system to attack existing cancerous cells. Those most commonly being investigated throughout the world are tumour cell or whole cell, dendritic cell, DNA and anti-idiotype vaccines. (American Cancer Society, 2000).

Tumour cell vaccines

Tumour cells are removed from the patient (autologous) or from another person's whole or inactivated tumour cells (allogenic). The cells are then grown in the laboratory and the tumour cells killed (usually by radiation) to ensure the cells can no longer multiply. Antigens remain on the tumour cell surfaces and when the whole tumour cells are injected into the cancer patient, they stimulate a specific immune response - cancer cells carrying these antigens are recognised and attacked. These types of vaccines are expensive to process but have been used to treat a number of cancers, in particular melanoma, renal and colorectal cancers (American Cancer Society, 2000).

Dendritic cell vaccines

For these vaccines, dendritic cells are removed from the patient's blood and reproduced in cell cultures. The cultured dendritic cells are then exposed to antigens from the surface of the patient's cancer cells and the dendritic cells and antigens are then injected back into the patient's body. The whole process is very similar to giving someone a blood transfusion with his or her own blood cells.

The 'trained' dendritic cells then help the immune system to recognise cancer cells in the patient's body that carry the antigen, and stimulate a normal immune response to the tumour, letting the body's T-cells kill the cancer cells.

Early studies of dendritic cell vaccines have shown promising results, especially with cancers of the ovary, prostate, colon, skin and lung.

DNA vaccines

Every chemical, including the antigens on cancer cells, has a part of DNA code that instructs the cells what to make. Scientists have developed a way to inject parts of DNA code into a person with cancer that instructs the patient's cells to produce certain antigens continuously. These therapies have been used with some success against melanoma.

Preventive vaccines

Although preventive cancer vaccines are not generally available, they hold out the greatest potential benefit. Trials are in progress with a vaccine aimed at the Human Papilloma Virus (HPV), the main cause of cervical cancer.

Conclusion

Vaccine therapy is still in its infancy, but there is evidence it could benefit patients in the future. While scientists believe a third of all cancers could be prevented with lifestyle changes, such as maintaining a healthy diet and eliminating tobacco, they also hold out hopes for vaccines. Their use in preventing and curing cancers that are not responsive to lifestyle changes in lifestyle is the dream of both scientists and cancer patients.

USEFUL WEBSITES

The American Cancer Society

www.cancer.org

The National Cancer Institute of America

http://rex.nci.nih.gov

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