Biologic therapies (biotherapy) focus on the body's biological response to the tumor. Most of these therapies take advantage of the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that may be caused by some cancer treatments.

How Does the Immune System Work?

In order for cancer to succeed, it must contend with the immune system. The immune system consists of a complex network of cells and organs that work together to defend the body against invaders, like bacteria and viruses.

The key cells involved in the immune system include:

  • Lymphocytes—This type of white blood cells are concentrated in areas of the body that commonly encounter hostile invaders (eg, gastrointestinal system, respiratory system, lyphatic system). Types of lymphocytes include:
    • B cells—lead to the production of antibodies
    • Cytotoxic T cells—directly attack infected or cancer cells
    • Helper T cells—regulate the immune system's response by signaling other immune system cells
    • Natural killer (NK) cells—produce powerful chemical substances that bind to and kill invaders
  • Macrophages—a type of white blood
  • Cytokines—chemicals produced by both lymphocytes and monocytes; examples include:
    • Interferons
    • Interleukins
    • Colony-stimulating factors

Macrophage

Macrophage
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How Do Biologic Therapies Work?

Biologic therapies repair, stimulate, or enhance the body’s response to cancer. According to the Leukemia and Lymphoma Society, biologic therapies:

  • Eliminate, regulate, or suppress conditions that allow uncontrolled cell growth
  • Enhance the immune system to fight the uncontrolled growth of cancer cells
  • Make cancer cells more vulnerable to destruction by the immune system
  • Change the growth patterns of cancer cells so that they are more like normal cells, and are less likely to metastasize (spread)
  • Block or reverse the process that changes a normal or precancerous cell into a cancerous cell
  • Enhance the body's ability to repair normal cells that get damaged by other forms of treatment for cancer (eg, chemotherapy, radiation therapy)
  • Prevent a cancer cell from spreading to other parts of the body

What Are Biologic Therapies Used for?

Biologic therapies are most commonly used either to treat cancer that does not or has not responded to other forms of treatment or to try to treat tumors that may respond to the body’s own immune defenses.

What Are the Major Types of Biologic Therapies?

The most common biologic therapies include:

  • Interferons (IFN)
  • Interleukins (IL)
  • Colony-stimulating factors (CSF)
  • Monoclonal antibodies (MOAB)

Interferons

Interferon (IFN) occurs naturally in the body. IFN is produced by virally infected cells and is capable of protecting other cells from infection. There are three major types:

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.

Interleukins

Like interferons, interleukins (IL) occur naturally in the body and can be synthesized in a lab. Interleukins are named numerically: IL-1, IL-2, IL-3, up to IL-18.

IL-2 has been the most widely studied in cancer treatment. This type of interleukin 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 (Proleukin) is an IL-2 that is used to treat kidney cancer and melanoma.

Colony-stimulating Factors

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 (Neupogen) and GM-CSF (Leukine, Prokine)—increase the number of white blood cells, which reduces the risk of infection; also used to stimulate the production of stem cells in preparation for stem cell or bone marrow transplants
  • Erythropoietin (Epogen, Procrit)—increase the number of red blood cells and reduce the need for red blood cell transfusion
  • Oprelvekin (Neumega)—increase the number of platelets and reduce the need for platelet transfusions

Monoclonal Antibodies

Monoclonal antibodies (MOABs) 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 caner.

MOABs can be used in cancer treatment in a number of ways, for example:

  • React with certain types of cancer, which may enhance the 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
  • Possibly help destroy cancer cells in bone marrow (during the process of bone marrow transplant)

There are a number of MOABs available, such as:

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

What Are the Side Effects?

The side effects depend on the type of biologic therapy that is used.

Interferons

At the beginning of therapy, you will most likely experience flu-like symptoms. Examples include chills, headaches, muscle pain, 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 (eg, chills, fever, fatigue, headache, muscle pain, joint pain)
  • Gastrointestinal effects (eg, nausea, vomiting, diarrhea, decreased appetite)

Other side effects include:

  • Skin—redness, rash, dry skin, itchiness
  • Heart and lungs—low blood pressure, rapid heart rate, arrhythmia, edema (fluid retention), weight gain
  • Nervous system—confusion, disorientation, drowsiness, lethargy, anxiety, depression, irritability
  • Decreased blood counts—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 effect.

Monoclonal Antibodies

With MOABs, allergic reaction to mouse protein is a major concern. The acute reaction can result in anaphylaxis, a severe, sometimes life-threatening, allergic reaction. This is rare, though.

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