3F8 Monoclonal Antibody Therapy Q & A

A person's immune system makes antibodies to attack germs such as bacteria or viruses, but it will not attack neuroblastoma because the tumor is part of our own bodies. An antibody that attaches to neuroblastoma can be made in a laboratory and then given intravenously to a patient. This antibody will circulate in the bloodstream until it finds and attaches to a neuroblastoma cell. And then the patient's own immune system will attack and kill that neuroblastoma cell.

3F8 is the name of a substance called a monoclonal antibody. It attaches to GD2, which is a marker on the surface of neuroblastoma cells. 3F8 was produced by white blood cells of mice, and it must be carefully prepared for human use. 3F8 is part of our standard treatment for high-risk neuroblastoma and is only available at Memorial Sloan-Kettering.

When 3F8 is injected into a patient's bloodstream, it travels and attaches to the GD2 marker on neuroblastoma cells. The attachment of 3F8 to a neuroblastoma cell serves as a signal to the patient's own immune system (for example, the white blood cells) to attack the tumor cell and kill it. In other words, the 3F8 directs the patient's own immune system (which usually acts only to control infections) against the neuroblastoma. Chemotherapy weakens a lot of the immune system, but not the part that works with antibodies. With time, as the body's own immune system becomes stronger, 3F8 treatments may help the body learn to fight tumors on its own.

We have attached a radioactive isotope called 131-iodine (131I) to 3F8 and injected the 131I-3F8 into patients. Then, when patients are scanned (just like with a bone scan or MIBG scan), we see radioactivity (from the 131I-3F8) in areas we know contain neuroblastoma but not in other areas in the body.

Since 1986, more than 18,000 infusions of 3F8 have been safely used in more than 400 patients. Through the years,  we have learned how to use 3F8 in order to make it better for killing neuroblastoma.

3F8 is given intravenously (IV) over 30 minutes through a Broviac, Hickman, MediPort, or peripheral line. When being treated with 3F8, patients usually need to be in the clinic for about three hours. This period includes time for giving medicines to prevent possible side effects, the 30 minute 3F8 treatment itself, and one to two hours to monitor the patient for side effects.

Pain is the main side effect. All patients have pain. The second most common side effect is rash (hives with itching), which is an allergic reaction. Pain can lead to a fast pulse (rapid heart rate) and sometimes causes high blood pressure for a short period. Less-common side effects include fever, vomiting, and diarrhea. These problems can usually be taken care of in the outpatient clinic, but sometimes a patient needs to be admitted to the hospital for an overnight stay. In the neuroblastoma outpatient clinic at Memorial Sloan-Kettering, we routinely treat 10 to 12 patients a day with 3F8, and manage side effects of the treatment without much difficulty.

3F8 attaches to GD2, which is present on some nerve cells as well as on neuroblastoma cells. When 3F8 attaches to a nerve cell, a message is sent to the brain, and the patient feels pain. The pain usually starts toward the middle or end of the daily 3F8 treatment and lasts a short time (usually from a few minutes up to an hour). Sometimes discomfort or minimal pain continues during the hours after the treatment. Medicines are used to prevent or control the pain (usually morphine or Dilaudid) and the allergic reactions (usually Benadryl or Vistaril). Ativan and Zofran are other medicines that can help. Patients who were treated with 3F8 beginning in 1986 have been followed, and to date, no permanent side effects on their nerves have appeared.

HAMA stands for "human anti-mouse antibodies." HAMA measures how strongly the body's immune system is reacting to 3F8. 3F8, like most monoclonal antibodies, comes from a mouse white blood cell. This means that 3F8 looks different from a human antibody, and a human will form antibodies (HAMA) against 3F8. If a patient has HAMA, there is no point in doing 3F8 treatments because the HAMA will block the 3F8 from getting to neuroblastoma cells. However, HAMA can disappear, and 3F8 treatments can then resume. Patients are checked for HAMA by means of a blood test. Patients with HAMA do not have pain or other side effects of 3F8 treatment, but patients without side effects sometimes do not have HAMA (and can continue to be treated with 3F8).

HAMA might be a sign that a patient is developing an immune response against the neuroblastoma -- and that is a good thing. It is probably best that a patient receive at least four cycles of 3F8 treatments. Most patients who have received chemotherapy only a short time before 3F8 treatment do not make HAMA because part of their immune system is too weak. In Memorial Sloan-Kettering's protocols, the aim is to give repeated treatments with 3F8 until HAMA is made. It appears that the best chances for cure are realized when multiple cycles of 3F8 treatment are given before the patient begins to form HAMA. We continue to study HAMA to gain a better understanding of its role.

No. An outside company produces it under GMP (good manufacturing practice) conditions. Private funding is needed to pay for the production of 3F8 and to carry out tests to meet the many safety requirements of the federal government. Patients are not charged for 3F8. While government (grant) funding has been given for much of the laboratory science involved with 3F8, the government generally does not support the manufacturing process.

We have 3F8 protocols for almost any patient who has high-risk neuroblastoma. [See our online clinical trial database for eligibility criteria and other information about specific protocols.]

It is best for a patient to start 3F8 treatment by six-to-eight weeks after transplant or after strong chemotherapy.

There are a number of phase I and phase II studies, as well as state-of-the-art chemotherapy currently being offered at Memorial Sloan-Kettering. Several promising approaches are in the pipeline waiting to be introduced into the clinic. See our online clinical trial database for current information.