Taking advantage of the body's healing power.

• Author: Ward, Darrell E.

A QUOTE by 18th-century surgeon John Hunter hangs above the desk of Steven Rosenberg, chief of surgery at the National Cancer Institute: "Surgery is like an armed savage which attempts to get by force that which a civilized man would get by stratagem." That notion is one of the guiding forces in Rosenberg's research. His mission is to civilize the treatment of cancer; his stratagem is immunotherapy--the use of the immune system to destroy a malignancy.

"The chief advantage of immunotherapy is that it uses the body's own immune system, a system that evolved to detect exquisitely small changes in molecules to tell nonself from the body. If we can take advantage of that system, we're more likely to have a treatment that is effective and carries minimal side effects," he explains.

It is one of the newest and most exciting areas of experimental cancer therapy. Research in immunotherapy is producing and using the most current knowledge of the immune system and the latest advances in molecular biology and gene therapy. The field gradually is earning a place alongside surgery, radiation, and chemotherapy for the treatment of the disease. More than a dozen clinical studies under way at Ohio State University's Arthur G. James Cancer Hospital and Research Institute provide some form of immunotherapy to certain patients.

"In selected patients, immunotherapy works," notes Pierre Triozzi, associate professor of internal medicine and director of the Biological Response Modifier Program at The James. "We've seen good responses in 15 to 20% of patients we've treated."

Through the use of vaccinations, the immune system has been used very successfully by medical science to fight infectious disease. "And I don't think immune therapy for cancer is a pipe dream at all," says Julian Kim, clinical instructor of surgery at The James. "It's a matter of understanding cancer a little bit better to enable the immune system to target cancer cells."

The key to making immunotherapy succeed lies in helping the immune system to recognize malignant cells as defective tissue. The immune system does this already when cells are infected with a variety of viruses. There is circumstantial evidence that cancer cells form throughout life, but are destroyed by the body before they become dangerous. Yet, more than 1,000,000 Americans get cancer each year--obvious evidence that malignant cells somehow gain the upper hand and elude detection by the immune system.

The immune system is the body's first line of defense against viruses, bacteria, fungi, toxins, and foreign cells. It is fully capable of destroying tissue, which is what happens during rejection of a transplanted organ and during autoimmune diseases. In the latter, the immune system mistakenly kills normal, healthy tissues in the body. This occurs in rheumatoid arthritis and some forms of diabetes.

The fundamental job of the immune system is to distinguish what belongs in the body from what doesn't--to recognize self from non-self, as the scientists say. The work is done by white blood cells, including monocytes, macrophages, cosinophils, and basophils. The bulk of the immune response is carried out by the group of white blood cells known as lymphocytes.

Through a microscope, lymphocytes are medium-sized, round cells in which the nucleus is offset like the yolk in a hard-boiled egg. They all look alike, but, on closer inspection, using sensitive biochemical tests, important differences emerge.

For example, most immune cells fall into one of two main camps: B or T cells. B cells, which make up about 25% of immune cells, take their name from the fact that they develop and mature in bone marrow. Their job is to produce antibodies--proteins tailor-made to attach to an antigen, a molecule that identifies a virus, bacterium, or foreign cell as non-self. Each B cell can recognize only a single antigen.

Once activated, a B cell begins dividing and producing antibodies, churning out as many as 2,000 antibody molecules a second for several days. The antibodies are carried throughout the circulatory system, binding to their antigens upon contact...