Medically Reviewed On: July 11, 2008

JOHN LEONARD, MD: Antibodies are naturally made by our immune system to fight infections. So we have, circulating in our blood and throughout our body, proteins or antibodies, that bind to specific targets on infections. They're made by our immune system in response to infections.

ANNOUNCER: Beginning in the 1970s, scientists began looking for ways to use artificial antibodies to fight cancer by targeting proteins on the surface of cancerous cells. One hurdle was to find targets that were not too widely distributed throughout the body, on healthy cells. The type of cancers known as lymphomas had a clear advantage for this research.

JOHN HAINSWORTH, MD: Lymphomas have been for a long time recognized as a group of cancers that are perhaps more amenable to this because they do have specific surface proteins that, if not entirely specific to the lymphoma, at least are very limited to this one group of cells in the body.

ANNOUNCER: One of those surface proteins is called CD20. It's found in most B-cell lymphomas, which are the most common type in non-Hodgkin's lymphoma.

JOHN LEONARD, MD: CD20 is a molecule; it's a protein that's present on the surface of B-cell lymphomas cells. The role or the function of this particular protein in the lymphoma cell is not very clear. But it is evident that the vast majority of patients with the B-cell type of lymphoma—again, the most common, general type—have this target on their lymphoma cells. And, therefore, an antibody that can bind to, can stick to this target and have a variety of different effects on the cell through this target, could result in shrinkage of the lymphoma and, obviously, a benefit to the patient.

ANNOUNCER: The therapeutics used to target the CD20 protein are artificial, or monoclonal, antibodies. They come in two forms: "Naked," which are monoclonal antibodies alone, and monoclonal antibodies that carry a radioactive material.

SANDRA HORNING, MD: Currently, there are three products that are on the market that we consider anti-CD20 monoclonal antibodies. The first is rituximab, also known as Rituxan, which is a naked or unconjugated antibody. And this was the first anti-CD20 antibody that was approved. There are also two conjugated antibodies that have radioisotopes. So these are also known as radioimmunotherapy. Both of them use the anti-CD20 mechanism for targeting. Both of them deliver radiation. These products are known as ibritumomab tiuxetan or Zevalin, or tositumomab, which is known as Bexxar.

ANNOUNCER: Most of the clinical research on monoclonal antibodies in lymphoma has focused on the naked type. Key studies in the mid-1990s showed rituximab improved outcomes for many patients with advanced disease.

JOHN HAINSWORTH, MD: The first studies with Rituxan were done in patients with low-grade lymphomas that had already had many other treatments. So these patients were not expected to respond well to further treatment. In those patients, half of them with this new drug had a major response: in other words, a shrinkage by at least 50 percent of their lymphomas. And the median duration of that was about 12 months.

Even now, eight years or nine years later, there are still about 10 percent of those patients from those first trials that have never had a progression of their lymphoma again. So this was an extraordinarily active drug.

ANNOUNCER: The studies also showed monoclonal antibodies have fewer side effects than chemotherapy.

JOHN LEONARD, MD: Antibody treatments generally don't affect the blood counts, don't cause hair loss, have minimal nausea. They're more associated with what we call infusion reactions: fatigue, fever, chills, shakes, while the patient is getting it. But, generally, they're relatively easy to take compared to many different chemotherapy regimens.

ANNOUNCER: On the basis of the early studies, rituximab was approved for use in low-grade or follicular lymphomas that had relapsed or which proved resistant to other therapies. Now, rituximab is also being used by many doctors for initial therapy in low-grade disease, either alone or in combination with chemotherapy. In treating aggressive forms of non-Hodgkin's lymphoma, rituximab has been approved as initial therapy in combination with chemotherapy. Questions remain, however. Doctors say important research into how to best use monoclonal antibodies is still underway.

SANDRA J. HORNING, MD: We're still in the process of understanding how to best use them, but where they have been studied either alone or in combination with traditional cytotoxic therapies, either at the beginning of the disease or upon disease relapse or recurrence, even in combination with high-dose therapies such as autologous stem cell transplantation, efficacy has been noted.

And what has really been important about these antibodies, as opposed to many of the other therapeutics that have come along the line, is that they are relatively nontoxic, and you can combine them with traditional cytotoxic therapies, but you don't have to reduce the dose or alter the schedule of the pre-existing effective treatments. Therefore, the combination has proven to be safe and more effective in essentially every setting in which it's been tested in both indolent and aggressive lymphomas.