It is known today that the human body has immune defenses against cancer, and that these defenses may (1) eliminate cancer before it becomes established, (2) attack cancer cells after they become established, and (3) occasionally (rarely) completely eliminate an established cancer to bring about spontaneous cure.

Because cancer cells have defenses against immune-system attack, they are often able to evade the body’s attempt to slow or halt the growth of cancer cells.

The purpose of biotherapy is to put laboratory-produced versions of naturally-occurring molecules into the body, to enhance the body’s defenses against cancer.

Biotherapy, chemotherapy and radiologic therapy (X-rays and radioisotopes) are used only in more advanced stages of melanoma. Surgery is the primary and most effective treatment for melanoma that (1) is confined to outer layers of the skin, and (2) has not undergone metastasis (spreading to other parts of the body). (Click on Thickness for a discussion of the relationship between melanoma thickness and melanoma severity).

An important note about biotherapy: While several biotherapeutic agents are currently approved for use, numerous others are in various stages of clinical trial. Biotherapy is a rapidly developing field that will bring numbers of new agents into use over the next several years.

Modern biotechnology makes biotherapy possible by producing the naturally-occurring molecules in a laboratory, and making them available in a therapeutically-useful form. The major biotherapies in clinical or investigative use today include:

• cytokine therapy (interferons, interleukins)
• adaptive cellular therapy
• monoclonal antibody therapy
• vaccine therapy

Cytokine Therapy

Cytokines hold enormous potential for cancer therapy, and many cytokines are under study as therapeutic agents while others are in current use. Management of side effects is one of the problems in cytokine therapy.

Interleukins and interferons are the cytokines in current use as biotherapeutic agents.

Cytokine is a word used to describe a large group of molecules that mediate (regulate) interactions in the immune system. These "mediators" are messengers that carry biochemical signals to regulate local and systemic immune responses, inflammatory reactions, wound healing, formation of blood cells, and many other biologic processes. More than 100 cytokines have been identified.

A number of cytokines have been of interest in cancer therapy, based upon observation of their ability to enhance immune responses to cancer cells. Because of multiple side effects, cytokine use must be carefully monitored.

Immunoregulatory cytokines of interest in cancer therapy include:

Interleukins are identified by number as IL-1, IL2, IL-3, etc., some of which activate antibody and cellular "killer" activities of specific white blood cells. The side effects associated with interleukins suggests that they should be administered only in a medical center with experience in their use.

Interferons, a group of cytokines that has been successfully adapted to anti-cancer therapy. Interferons also are used in anti-viral treatment—for example, in treatment of hepatitis B and C. On the basis of their chemical structure, biologic activities, and other criteria, interferons are classified as alpha, beta or gamma forms. Interferon-alpha is the form used in treatment of metastatic melanoma because of its activity in slowing the proliferation of tumor cells. Interferon-alpha is sometimes used in combination with chemotherapy. The most commonly reported side effect of interferon therapy is flu-like symptoms including headache, fever and a generalized feeling of illness.

Until quite recently, neither biotherapy nor chemotherapy were effective in increasing long-term survival of more than small numbers of patients with metastatic melanoma. Combinations of chemotherapy and biotherapy have begun to show some more optimistic results, both in response of tumors to combined therapy and in improved survival of patients. The number of patients involved is still small, making it difficult to generalize from a limited number of optimistic results to projection of results for individual patients.

Persons interested in keeping up with publication of melanoma studies in medical journals can log on to MedLine, the electronic archival service of the National Library of Medicine, at: http://www.nih.gov/.

Those interested may also discuss with their physicians the possibility of entering clinical trials of drugs under investigation.

Adaptive Cellular Therapy

Still largely experimental, this form of therapy involves taking anti-tumor-specific white blood cells from the patient, treating them to make them active, then putting them back into the patient to attack tumor cells. Adaptive cellular therapy is still in experimental stages.

Monoclonal Antibody Therapy

Melanomas are known to produce molecules that can be recognized and attacked by the immune system. When a molecule has this sort of immune recognition it is called an "antigen". When a tumor antigen is on the surface of a melanoma cell, it may render the melanoma open to immunologic attack by antibodies.

Monoclonal antibodies are antibodies produced in the laboratory and biotechnologically engineered to "lock on" to specific antigens. One purpose of "locking on" is to kill the tumor cell by antitumor activity. Monoclonal antibodies also can be tagged with radioisotopes and used as "beacons" in diagnosis and in planning of treatment.

Monoclonal antibody therapy is still in experimental stages in treatment of melanoma.

Vaccine Therapy

An effective melanoma vaccine would be a great boon. It would make the immune system capable of recognizing specific melanoma antigens and eliminating melanoma cells, much as mumps vaccine makes the immune system capable of recognizing mumps antigens and eliminating mumps virus in the body before it causes disease. A vaccine against a patient’s own melanoma could, in theory, immunize the patient against recurrence or metastasis of the melanoma. No melanoma vaccine has been approved for human use, but many investigators are working on vaccine development.

Biotherapy in Summary

Biotherapy is a newer form of cancer treatment that shows great promise. There are currently more biotherapeutic agents in development and trial than there are in use. Those in use have been effective enough to justify further research and development.