Biological therapy for cancer

ALSO KNOWN AS: Immunotherapy, biological response modifier therapy, biotherapy, biologic agents, biologic therapies, biologicals

DEFINITION: Biological therapy is an emerging, growing class of cancer drugs that work to help optimize the ability of the body’s immune system to fight cancer or other diseases, or to help lessen side effects from other cancer treatments such as chemotherapy.

Cancers treated: A number of cancers, including melanoma, leukemia, breast, ovarian, colon, lung, and kidney cancers

Subclasses of this group: Cytokines, monoclonal antibodies, colony-stimulating factors, antiangiogenesis agents, cancer vaccines

Delivery routes: The delivery route varies depending on which biological therapy is being used. Various biological therapies may be given by mouth, by intravenous (IV) drip (infusion), by subcutaneous or injection, or by delivery directly into a body cavity to treat a specific site.

How these drugs work: The cells, antibodies, and organs of the immune system work to protect and defend the body against foreign invaders, such as bacteria or viruses. The immune system is a complex network of cells and organs that work together in a variety of ways. White blood cells are a very important part of the immune system. Lymphocytes are a type of white blood cell found in the blood and many other parts of the body that are intimately involved with the way that most biological agents work. Types of lymphocytes include B cells, T cells, and natural killer (NK) cells. B cells mature into plasma cells that secrete proteins called antibodies, which recognize and attach to foreign substances known as antigens. Each type of makes one specific that recognizes one specific antigen. T cells produce proteins called cytokines, which include interferons, interleukins, and colony-stimulating factors. Cytokines are proteins that activate the immune system and that play an important role in communication between immune system cells. NK cells produce powerful cytokines that attach to and kill many foreign invaders, infected cells, and cancerous cells.

Advances in techniques of molecular biology since the 1980s have brought about a revolution in the understanding of many biological processes at a molecular level, including mechanisms involved in immunity and the pathogenesis of many diseases. In many cases, it has become possible to identify discrete, specific molecular targets for therapeutic intervention and to design therapies to block or interact with those targets. At the same time, technological advances have made it possible to engineer and to produce these targeted therapeutic molecules for medical use.

Physicians and researchers have found that, in addition to protecting the body against foreign invaders, the immune system might be able to differentiate between healthy cells and cancer cells in the body and to eliminate cancerous ones. Biological therapies are designed to repair, stimulate, or enhance the immune system, either directly or indirectly, by assisting in the following ways: making cancer cells more recognizable by the immune system, boosting the killing power of immune system cells, changing the way in which cancer cells grow such that they act more like healthy cells, stopping the process that changes a normal cell into a cancerous cell, enhancing the body’s ability to repair or replace normal cells damaged or destroyed by other forms of cancer treatment such as chemotherapy or radiation, and preventing cancer cells from spreading to other parts of the body.

Biological therapies involve molecules that the body normally makes in small amounts in response to infection and disease and the use of modern recombinant deoxyribonucleic acid (DNA) technology to produce these molecules in large amounts for use in the treatment of cancers and other diseases. Molecular splicing of genes or portions of genes of interest to form DNA sequences that code for recombinant or fusion proteins is performed. These recombinant DNA sequences are spliced into plasmid vector molecules that can be introduced into host cells, which can then be used in scaled-up production of large amounts of the purified recombinant or fusion protein.

Important types of biological therapies are cytokines (interferons and interleukins), monoclonal antibodies, growth factors, colony-stimulating factors, antiangiogenesis agents, and cancer vaccines.

Interferons were the first cytokines to be produced in the laboratory for use as biological therapies. Several types of inferons occur naturally in the body, of which interferon alpha is the most widely used in cancer treatment. Interferons can improve the immune system function against cancer cells and may, in addition, directly slow the growth of cancer cells or promote their development into cells with more normal behavior. There is some evidence that interferons may also stimulate NK cells and T cells, thereby boosting the immune system’s function against cancer cells. Intron A (interferon alpha) has been approved by the Food and Drug Administration (FDA) for cancer treatment; it is used for the treatment of hairy cell leukemia, melanoma, chronic myeloid leukemia, and AIDS-related Kaposi and non-Hodgkin lymphoma.

Interleukins are also cytokines that occur naturally in the body. Many types have been identified. Interleukin-2, which stimulates the growth and activity of many immune cells which can destroy cancer cells, has been the most widely studied in cancer treatment. Proleukin (interleukin-2) has been approved for use in the treatment of metastatic and metastatic renal cell carcinoma.

Monoclonal antibodies are a single species of antibody that is produced in the laboratory from a single type of cell and is specific for a particular antigen. The production of monoclonal antibodies involves the creation of a hybrid cell line specific for that antibody molecule, called a hybridoma. Once produced, a hybridoma can be perpetuated in the laboratory to produce as much of the pure monoclonal antibody as desired. Monoclonal antibodies may be used in several ways. They may be used to boost the immune response to cancer cells, they may be designed to act against growth factors to inhibit the growth of cancer cells, and they may be linked to anticancer drugs, radioactive substances, or toxins to act as a vector to deliver these toxic agents directly to cancer cells. Rituxan (rituxamab) and Herceptin (trastuzumab) are examples of monoclonal antibodies that the FDA has approved, Rituxan for the treatment of non-Hodgkin lymphoma and Herceptin to treat metastatic breast cancer.

In 2024, the FDA approved Mirvetuximab soravtansine-gynx (Elahere) as a treatment for patients with advanced, platinum-resistant ovarian cancer whose tumors produce excessive amounts of FR-α. This antibody-drug conjugate is made up of a monoclonal antibody called mirvetuximab, which is attached to a highly potent chemotherapy drug, DM4. Mirvetuximab seeks out and binds to FR-α on the surface of ovarian cancer cells. The drug is then pulled into the cancer cell where the DM4 is released. This kills the cancer cells but leaves the healthy, normal cells mostly intact.

Colony-stimulating factors (CSFs) stimulate bone marrow cells to divide and develop into white blood cells, red blood cells, and platelets. CSFs may be helpful for some patients undergoing treatment for cancer because many anticancer drugs used in chemotherapy can damage the body’s ability to make these important cells in the bone marrow. Thus, patients receiving chemotherapy have an increased risk of developing infections, anemia, and bleeding more easily. The dose of chemotherapy that a patient receives, and therefore the chemotherapy regimen’s effectiveness in fighting cancer, can sometimes be increased by using CSFs to eliminate or reduce the risk of infection or the need for transfusions. Neupogen (filgrastim) and Procrit (epoetin alfa) are colony-stimulating factors that the FDA has approved for use in cancer patients, Neupogen to boost the number of white blood cells during chemotherapy and Procrit to boost the number of red blood cells during chemotherapy.

Antiangiogenesis agents, also called angiogenesis inhibitors, are an emerging type of biological therapy that show promise in fighting cancer. Cancer cells are rapidly dividing cells that depend on a rich network of small blood vessels to supply them with oxygen and nutrients. Tumors must generate this network of new blood vessels, a process called angiogenesis. Several types of molecules and antibodies have been shown to prevent angiogenesis and shrink tumors. Avastin (bevacizumab) is an monoclonal antibody that has been approved for the treatment of lung and cancers.

Cancer vaccines are another type of biological therapy being studied. Vaccines for infectious diseases work by exposing an uninfected individual to a weakened form of the infectious agent. The vaccine stimulates the immune system to mount an immune response to the agent but cannot cause the disease. The immune system produces antibodies specific to antigens present on the surface of the infectious agent. The immune system is also stimulated to produce certain types of T cells, which remember the exposure to the antigen. If the individual is subsequently challenged with the same infectious agent, then these T cells will orchestrate a quick and effective immune response, protecting the individual from contracting the disease. Cancer vaccines to treat existing cancers (therapeutic vaccines) or to protect healthy individuals from developing cancer (prophylactic vaccines) are being studied. Therapeutic vaccines may be effective in stopping the growth of existing cancer cells, in preventing cancer from recurring, or in killing existing cancer cells. Prophylactic vaccines are administered to healthy individuals to protect against cancers that are caused by viruses. As of 2023, the FDA had appoved three different therapeutic vaccines, which are bacillus Calmette-Guerin (BCG) for the treatment of bladder cancer, Sipuleucel-T (Provenge) for the treatment of metastasized prostate cancer, and talimogene laherparepvec (T-VEC) for the treatment of melanoma. Gardisil (quadrivalent human papillomavirus recombinant vaccine) is a prophylactic vaccine that the FDA has approved for the prevention of cervical cancer caused by human papillomavirus.

Some biological therapies have been approved by the FDA for certain types of cancer, while many, still in development, are offered in clinical research studies to measure the effects of the treatment. In these cases, study results are often used as part of the FDA evaluation of the drug’s efficacy and safety.

Side effects: The side effects of biological therapy regimens are variable from patient to patient. The most common side effects are a result of stimulation of the immune system and are similar to flulike symptoms, including fever, chills, body aches, nausea, vomiting, loss of appetite, and fatigue. Some patients may experience a rash or swelling at the injection site. Most side effects diminish one to two days after treatment. For patients who receive multiple doses of a biological therapy, the side effects usually lessen over time.

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