Immunotherapy

Immunotherapy, also called biological therapy, utilizes your own immune system to fight cancer. It generally results in fewer short-term side effects than chemotherapy does.

Immunotherapies being used or studied to treat blood cancer include:

• Chimeric antigen receptor (CAR) T-cell therapy
• Cytokine treatment
• Donor lymphocyte infusion
• Monoclonal antibody therapy
• Radioimmunotherapy 
• Reduced-intensity allogeneic stem cell transplantation
• Therapeutic cancer vaccines 

Doctors use immunotherapy in several different ways to treat blood cancers, including:

• In combination with other types of cancer treatment
• As maintenance therapy after combination chemotherapy
• As a single agent 

Cancer and the Immune System

The body’s immune system helps protect us against disease and infection. It includes a network of cells and organs that help defend the body from "antigens” — foreign substances such as bacteria, viruses, fungi, harmful toxins and allergens. When antigens are ingested or come into contact with the skin or mucous membranes, they stimulate an immune response: White cells produce antibodies that "coat" the antigens, marking them as targets for other white cells or inactivating the antigens. The other white cells then attack and destroy the antigens.

In most circumstances, the body's natural immune system seems unable to identify cancer as a foreign invader. One reason for this may be that cancer cells aren't external invaders like viruses and bacteria are. Instead, cancer cells are altered versions (mutations) of normal cells and don't produce a unique feature like an antigen that will trigger an immune response. What's more, cancer cells may also suppress immunity, which may contribute to the immune system's failure to recognize cancer cells as foreign invaders.

Immunotherapy is based on the concept that immune cells or antibodies that can recognize and kill cancer cells can be produced in the laboratory and then given to patients to treat cancer. Several types of immunotherapy are either approved for use by the Food and Drug Administration or are under study in clinical trials to determine their effectiveness in treating various types of cancer.

Immunotherapy Treatment Approaches

Researchers are studying immunotherapy with three general approaches:

• Immune cells from the patient or a transplant donor are used to attack residual leukemia, lymphoma or myeloma cells that remain after chemotherapy.
• Manmade antibodies are able to attach to antigens on the cancer cell, using samples of tumors.
• Vaccines are being developed that may suppress cancer cells left in the body after therapy and thereby prolong remission.

Types of Immunotherapies 

Chimeric antigen receptor (CAR) T-cell therapy

This is a type of immunotherapy. The patient cells are removed through apheresis and modified in a laboratory so they can be reprogrammed to target tumor cells through a gene modification technique. The cells are then returned to the patient following chemotherapy. To read more about this treatment, currently in clinical trials, please click here. 

Cytokine Treatment

Other treatments used to stimulate the immune system in a general way and used in combination with monoclonal antibodies, vaccines or chemotherapy are substances called cytokines — hormones produced by the body that help the immune system function. Manmade cytokines are used as an adjunct (additional) therapy to boost the immune system. Examples of these treatments are:

• Granulocyte-macrophage colony-stimulating factor (GM-CSF)
• Interleukin-2 (IL-2)
• Interferon

Donor lymphocyte infusion

Some blood cancer patients, especially those with chronic myeloid leukemia (CML), who have a relapse after stem cell transplantation or for whom transplantation isn't successful, may benefit from an immune cell treatment called donor lymphocyte infusion.

During this procedure, doctors transfer lymphocytes (a type of white cell) from the original stem cell donor's blood to the patient. The infusion's goal is to attack or suppress leukemia cells by inducing an intense immune reaction against the patient's cancer cells. This is called a graft versus tumor (GVT) effect.

Donor lymphocyte infusion has been helpful in treating relapsed CML after allogeneic bone marrow transplantation. It may also be a helpful treatment for patients with relapsed myeloma after allogeneic stem cell transplantation.

Monoclonal Antibody Treatment

Monoclonal antibody therapy is sometimes referred to as passive immunotherapy because it doesn't directly stimulate your immune system to respond to a disease. Instead, monoclonal antibody therapy mimics the natural antibodies made by the body.

A monoclonal antibody is an immune protein made in a laboratory. It's designed to react with or attach to antigens — foreign substances such as bacteria, viruses, fungi and allergens — on the surface of cancer cells. The monoclonal antibody aims for the molecule and attaches itself to the cell, blocking or interfering with the cell's activity. Because the drug attacks a specific target or marker on the cell, monoclonal antibody therapy is also called targeted therapy.

Monoclonal antibody therapies can cause side effects, but they're generally milder than those of chemotherapy. Because they're designed to target and attack specific substances, they tend to leave normal cells unharmed. Targeted treatment may also increase the frequency of and prolong remissions.

Doctors use monoclonal antibodies either alone or with another substance attached to them:

• Naked antibodies don't have another chemical or radioactive material attached. Rituximab (Rituxan®) and alemtuzumab (Campath®) are examples of naked monoclonal antibody therapy. The antibodies recognize and attach to specific cells. They can destroy the cancer cell when they attach to the cell's critical antigen.
• Conjugated antibodies have radioactive isotopes (radioimmunotherapy) or toxins (immunotoxin) attached to them. Daunorubicin (Cerubidine®), doxorubicin (Adriamycin®), idarubicin (Idamycin®) and mitoxantrone (Novantrone®) are examples of conjugated antibody therapy. They deliver the toxic substance directly to the cancer cells and destroy them.

What to Expect

Monoclonal antibody therapies are generally given to individuals in an outpatient setting, usually over several weeks. The drug is delivered through a needle placed into a vein (intravenous infusion, or IV) in your arm. Your doctor may prescribe drugs before each infusion to reduce certain side effects. He or she regularly tests your blood between and after treatment is completed to look for other side effects.

Side effects such as fever and chills, tiredness, headache and nausea are among the most commonly reported reactions to Rituxan and Campath. Other less common, but more severe, side effects include shortness of breath, a drop in blood pressure, an irregular heartbeat, chest pain and low blood cell counts.

Radioimmunotherapy

Radioimmunotherapy is mainly used to treat lymphoma and lymphocytic leukemia. It combines a radioactive substance with a monoclonal antibody that's injected (infused) into your body. The monoclonal antibody targets, and sometimes reacts with, proteins on cancer cells called antigens. The radioactive molecule destroys the cells.

Monoclonal antibodies are immune proteins made in the laboratory. A common monoclonal antibody used for blood cancer is ibritumomab (Zevalin®).

Radioimmunotherapy has a less toxic effect on normal tissues than chemotherapy does. The treatment doesn't cause hair loss, often doesn't cause nausea and causes only mild degrees of fatigue and lowered blood counts. The recovery period is generally brief.

What to Expect

Your doctor may give you anti-nausea drugs before treatment to ward off nausea and vomiting, which some patients experience. You'll also be given iodide pills before receiving the radioactive iodine-linked antibodies. This prevents your thyroid gland from absorbing the radioactive iodine.

In most cases, patients are treated with Zevalin in an outpatient facility. Therapy is administered over the course of 1 to 2 weeks. Before the patient receives the treating dose of radioimmunotherapy, he or she will be given a preparatory intravenous (IV) infusion of the antibody. On treatment day, the patient receives the antibodies via infusion, but this time, within four hours following the infusion, the patient will receive the dose of the radiation. It takes about 10 minutes to administer the injection.

Occasionally, patients have a severe allergic reaction to the infusion. Discuss this and other risks with your doctor before treatment. Fever, chills and aches can occur after treatment. Your doctor may give you drugs to reduce these effects.

After Treatment

After treatment, you'll need routine blood work for a few months to ensure you have a full blood count recovery. Most patients have a mild to moderate decrease in blood cell production for a short time. If you had chemotherapy or external radiotherapy before radioimmunotherapy, you may have a greater degree of cytopenia (low blood counts).

Some patients have mild to moderate reactions that tend to be short-lived. These include:

• Low blood pressure
• Diarrhea
• Rash or swelling at the injection site

You must take certain precautions to protect the people around you from radiation exposure. Your doctor and nurse will explain the precautions, which aren't restrictive and are easy to understand.

Radioimmunotherapy works gradually, so it may take several months for cancer cells to die and tumors to shrink. Your doctor monitors the treatment's effects with physical exams and imaging tests such as computed tomography (CT) scans and positron emission tomography (PET) scans. Overall, radioimmunotherapy is usually well tolerated.

Clinical Trials

If you're interested in immunotherapy, discuss the treatment with your doctor to learn whether you're a candidate. If the treatment isn't available, your doctor may refer you to a clinical trial that's studying a form of immunotherapy. See our clinical trials page for more information.