HCL is a rarely seen cancer of cells known as B lymphocytes, which circulate in the blood and are part of the body’s immune system. It is diagnosed in only 500 to 600 patients every year in the US, accounting for about 2 percent of leukemia cases. Several therapies are available for the treatment of patients with HCL. While current treatments can cause the cancer to go into remission, they cannot cure it because a small percentage of cancer cells are left behind after treatment. In addition, the treatments stop working after a period of time in about 10 to 20 percent of patients.

How The Treatment Works

The new experimental therapy involves the injection of an immunotoxin designed to destroy the cancerous cells. This immunotoxin, known as LMB-2, is made by using recombinant DNA technology to attach part of an antibody molecule (designed to recognize a substance called CD25) to the toxin produced by a bacteria called Pseudomonas.

Antibodies made in our bodies can recognize microbes and some cancer cells as "foreign," or "non-self." Once an antibody attaches to a microbe, the microbe is usually destroyed by immune system cells. But this system is less effective in killing cancer cells. LMB-2 is much more destructive to cancer cells because it has a deadly toxin attached to it. When the immunotoxin is injected into the body, its antibody position recognizes CD25 molecules of cancerous cells. The toxin then enters and destroys those cells.

"This treatment may be an effective new therapy for patients with this type of cancer," concluded the researchers. All four patients studied showed what the researchers described as "major responses." None of them were responsive to the standard therapies but they all responded to the immunotoxin after only one round of treatment. One of the four patients was treated twice with the immunotoxin and went into complete remission (meaning no cancerous cells were thought to be remaining). This patient had not relapsed after 11 months. The three other patients showed a dramatic 98 percent to 99.8 percent reduction in the number of cancerous cells in their bloodstreams.

"We are very excited by these results and optimistic that our approach will be useful for treating other types of cancer. The next step involves further research in more patients, which should begin next year," said lead study author Ira Pastan, MD, chief of the laboratory of molecular biology in the division of basic sciences at the National Cancer Institute.

Therapy Could Apply to Any Type of Cancer

The potential use for this type of therapy is not limited to HCL. Dr. Pastan predicts future research will show immunotoxins are potentially useful for any type of cancer as long as the cancer cells recognized by the immunotoxin are in some way different from normal, non-cancerous cells.
 
"Clinical trials using immunotoxins in patients with other types of cancer such as breast cancer, ovarian cancer, colorectal cancer, and melanoma are already underway," noted the author of a recent review on the subject, Louis M. Weiner, MD, of the Fox Chase Cancer Center in Philadelphia. But Dr. Weiner cautioned that "some studies have shown a toxic effect which is thought to arise from the uptake of the toxins by normal cells and further research needs to be performed."

Ralph Vogler, MD, scientific program director for the American Cancer Society (ACS) said there have been several different studies over the years on the ability of antibodies to target specific tissues. "The major problem is the specificity of the antibody.  If the antibody is made against a protein that is unique for the cancer cell, then it can be very effective with no toxicity. Overall, this is a promising approach."