Biologic Therapies for Cancer Treatment

Interferons

IFN occurs naturally in the body. IFN is produced by virally infected cells and is capable of protecting other cells from infection. Researchers have found that interferons enhance the immune system’s ability to fight cancer cells and act directly on these cells by slowing growth and encouraging normal cell behavior.

There are different types of IFNs, but interferon alpha is used to treat cancer. Currently interferon alpha is used to treat cancers including hairy cell leukemia, Kaposi's sarcoma, and chronic myeloid leukemia (CML).

Interleukins

Like IFNs, ILs occur naturally in the body and can be synthesized in a lab. ILs are named numerically as IL-1 through IL-18.

IL-2 has been the most widely studied in cancer treatment. This type stimulates the growth and activity of many cancer-killing immune cells, including NK cells and cytotoxic T cells. In addition, IL-2 enhances antibody responses.

Aldesleukin is an IL-2 that is used to treat metastatic kidney cancer and melanoma.

Colony-stimulating Factors

CSFs do not affect cancer cells directly. Instead, CSFs help stimulate the production of new red blood cells, white blood cells, and platelets. This is important because many cancer treatments can decrease the levels of blood cells, which increases the risk of infection, anemia, and bleeding problems. Stimulating blood cell production can help stimulate the immune system.

Some examples of CSFs include:

• G-CSF and GM-CSF—increases the number of white blood cells, which reduces the risk of infection; they can also be used to stimulate the production of stem cells in preparation for stem cell or bone marrow transplants
• Erythropoietin—increases the number of red blood cells and reduce the need for red blood cell transfusion
• Oprelvekin—increases the number of platelets and reduce the need for platelet transfusions

Monoclonal Antibodies

mAbs are substances that are produced in a lab. The process involves injecting a mouse with cells for a certain type of human cancer. Once injected with the cancer cells, the mouse produces antibodies to fight against the cancer. These mouse antibodies are then combined with other lab cells to create hybrid cells to fight cancer.

MAbs can be used in cancer treatment in a number of ways. They may:

• React with certain types of cancer to enhance the body's immune response
• Be programmed to act against specific cell growth factors to interfere with the growth of cancer cells
• Be linked to anticancer drugs, radioactive substances, other biologic therapies, or other toxins to tag the cancer cells and alert the immune system to destroy them
• Possibly help destroy cancer cells in bone marrow (during the process of bone marrow transplant)

There are a number of mAbs available, such as:

• Rituximab—used to treat non-Hodgkin's lymphoma
• Trastuzumab—used to treat breast cancer when the tumor expresses excess amounts of a protein called HER-2
• Cetuximab—used to treat colon and rectal cancers, as well as head and neck cancer
• Panitumumab—used to treat colon and rectal cancers
• Bevacizumab—used to treat a certain type of brain tumor and kidney, colon, rectal, lung, and breast cancers
• Alemtuzumab—used to treat chronic lymphocytic leukemia
• Ipilimumab—used to treat melanoma

Interferons

At the beginning of therapy, you will most likely experience flu-like symptoms, such as chills, headaches, muscle and joint pain, and discomfort.

Chronic side effects tend to increase in intensity after you have been on IFN therapy for several weeks. Loss of appetite with weight loss and fatigue can be severe enough to limit the dose. Other side effects include:

• Lack of energy
• Lack of concentration
• Decreased blood counts
• Protein in your urine
• Low blood pressure
• Less common side effects:
  • Nausea and vomiting
  • Diarrhea
  • Altered taste
  • Depression
  • Mood swings
  • Decreased sex drive
  • Memory problems

Interleukins

More common side effects include:

• Flu-like symptoms—chills, fever, fatigue, headache, and muscle pain and joint pain
• Gastrointestinal effects, such as nausea, vomiting, diarrhea, and decreased appetite

Other side effects include:

• Red, dry, or itchy skin, with or without a rash
• Low blood pressure, rapid heart rate, heart arrhythmia, fluid retention, and weight gain
• Confusion, disorientation, drowsiness, lethargy, anxiety, depression, and irritability
• Changes in blood cell counts that can lead to anemia, thrombocytopenia, eosinophilia, lymphopenia
• Problems with kidney function
• Hypothyroidism

Severe toxicities are associated with high doses of IL-2.

Colony-stimulating Factors

CSF therapy is generally well tolerated. The side effects are minimal. Bone pain is one of the most commonly reported side effects.

Monoclonal Antibodies

With mAbs, allergic reaction to mouse protein is a major concern. Rarely, the acute reaction can result in anaphylaxis, a severe, sometimes life-threatening allergic reaction.

More common side effects include:

• Fever
• Chills
• Sweating
• Discomfort
• Nausea and vomiting
• Itchiness
• Difficulty breathing
• Low blood pressure

A delayed toxicity that can occur is called serum sickness. Symptoms of serum sickness include:

• Hives
• Itchiness
• Joint pain
• Swollen glands
• Flu-like symptoms