Biological Therapies "Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body’s immune system to act against cancer cells. These types of biological therapy, which are sometimes referred to collectively as “immunotherapy” or “biological response modifier therapy,” do not target cancer cells directly. Other biological therapies, such as antibodies or segments of genetic material (RNA or DNA), do target cancer cells directly. Biological therapies that interfere with specific molecules involved in tumor growth and progression are also referred to as targeted therapies" (NCI Dictionary n.d.).
Immunotherapy is intended to restore or increase the anticancer activities of specific immune-system components or counteract immunosuppressive signals produced by cancer cells:
Immune checkpoint inhibitors are drugs that block immune checkpoint molecules on the surface of cancer cells. T-cells use checkpoint molecules to identify cells that are healthy "self" cells. Cancer cells often lose the ability to produce checkpoint molecules, or if a drug blocks a checkpoint, T-cells can recognize the cell as "non-self" and kill them.( Click to view video from Cancer.gov )
T-cell transfer therapy is a type of treatment in which a patient's T-cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T-cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer. Also called chimeric antigen receptor T-cell therapy.Monoclonal antibodies, which are immune system proteins created in the lab that are designed to bind to specific targets on cancercells.Somemonoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system. Other monoclonal antibodies bring T-cells close to cancer cells, helping the immune cells kill the cancer cells, e.g., blinatumomab (Blincyto®) binds to the CD19 protein found on the surface of leukemia cells, and the CD3 protein on the surface of T-cells. This process helps the T-cells get close enough to the leukemia cells to respond to and kill them. ("Click"NIH Monoclonal antibody video)
Treatment vaccines are different from the ones that help prevent disease. Cancer treatment vaccines can help the immune system learn to recognize and react to tumor associated antigens and destroy cancer cells that contain them. Cancer treatment vaccines may be made in three main ways:
- Autologous cell vaccine is made with the patient's own tumor cells processed in vitro, which may elicit a cytotoxic T-lymphocytic immune response against tumor cells antigens, resulting in tumor cell death (Gonzalez Marcano E. 2020).
- Allogenic cancer vaccine may be made from tumor-associated antigens that are found on cancer cells of many people with a specific type of cancer. To date there are no FDA approved allogenic cancer vaccines.
- Autologous cellular immunotherapy may be made from the patient's own dendritic cells, a type of phagocyte and a type of antigen-presenting cell (APC). Dendritic cell vaccines stimulate the immune system to respond to an antigen on the patient's tumor cells. One dendritic cell vaccine has been approved, sipuleucel-T, which is used to treat some men with advanced prostate cancer.
Sipuleucel-T is an FDA approved autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. It is made by collecting the patient's own dendritic cells by leukapheresis and incubating these cells with the antigen prostatic acid phosphatase (PAP) and granulocyte-macrophage colony stimulating factor. The cells are injected back into the patient where they stimulate T-cells to recognize and kill prostate cancer cells. Sipuleucel-T is a type of vaccine and a type of cellular adoptive immunotherapy. (Cancer treatment vaccines. n.d.).
Immune system modulators, which enhance the body’s immune response against cancer. Some of these agents affect specific parts of the immune system, whereas others affect the immune system in a more general way. Learn more about immune system modulators.
Cytokines are signaling proteins that are produced by white blood cells. They help mediate and regulate immune responses, inflammation, and hematopoiesis. Two types of cytokines are used to treat patients with cancer: interferons (INFs) and interleukins (ILs). A third type, called hematopoietic growth factors, is used to counteract some of the side effects of certain chemotherapy regimens.
Interferons (INFs). Researchers have found that one type of interferon, called INF-alfa, can enhance your immune response to cancer cells by causing certain white blood cells, such as natural killer cells and dendritic cells, to become active. INF-alfa may also slow the growth of cancer cells or promote their death.
Interleukins (ILs). There are more than a dozen interleukins, including IL-2, which is also called T-cell growth factor. IL-2 boosts the number of white blood cells in the body, including killer T-cells and natural killer cells. Increasing these cells can cause an immune response against the cancer. IL-2 also helps B cells (another type of white blood cell) produce certain substances that can target cancer cells.
Hematopoietic growth factors are cytokines that are used to reduce side effects from cancer treatment by promoting the growth of blood cells that are damaged by chemotherapy.
- Erythropoietin, which increases the production of red blood cells
- IL-11, which increases the production of platelets Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), which both increase the number of white blood cells. Boosting white blood cells reduces the risk of infections. G-CSF and GM-CSF can also enhance the immune system response against cancer by increasing the number of cancer-fighting T-cells.
Bacillus Calmette-Guérin (BCG) is a live mutant tuberculosis bacterium with reduced cytolytic capacity. It is only rarely used in the U.S. to prevent childhood TB. It is FDA approved for the treatment of bladder cancer. When inserted directly into the bladder with a catheter, BCG stimulates a general immune response against bladder cancer cells resulting in remission of bladder cancer in about 70% of patients.
Immunomodulatory drugs (also called biological response modifiers) stimulate the immune system.
They include:
- thalidomide (Thalomid®)
- lenalidomide (Revlimid®)
- pomalidomide (Pomalyst®)
- imiquimod (Aldara®, Zyclara®)
Thalidomide, lenaliodomide, and pomalidomide cause cells to release IL-2. They also stop tumors from forming new blood vessels. Tumors need to form new blood vessels to grow beyond a certain size. These three drugs may also be called angiogenesis inhibitors.
Oncolytic Viral therapy involves are a group of viruses that target, infect and lyse tumor cells. These viruses replicate in the tumor cells until the tumor cells rupture and die.Cell fragments from dead cells and autophagy dendritic cells activate immune response. The infected cancer cell may also release tumor-associated antigens to dendritic cells. The dendritic cell then induce T-cell adaptive antitumor immunity (Oncolytic 2022).
The first oncolytic virus to receive FDA approval was a treatment for melanoma known as talimogene laherparepvec (Imlygic®), or T-VEC. The treatment, which is injected into tumors, was engineered to produce a protein that stimulates the production of immune cells in the body and to reduce the risk of causing herpes. Talimogene laherparepvec is a novel herpes simplex virus (HSV-1) strain that has been genetically modified by deleting virulence genes and inserting two copies of human Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene sequences. The gene deletions increase destructive tumor-selective replication and insertion of GM-CSF gene enhances tumor antigen presentation to the immune system and induction of immune responses to the tumors.
References
Cancer treatment vaccines - immunotherapy. National Cancer Institute (NCI). (n.d.). Retrieved February 18, 2022, from https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/cancer-treatment-vaccines
Gonzalez Marcano, E., Kröhle, L., Ahlers, J., Drevs, J. (2020). Pilot study on outcome and antitumor efficacy of an autologous cancer cell vaccine applied in patients with advanced solid tumors. Journal of Clinical Oncology, 38(15_suppl), 3000–3000. https://doi.org/10.1200/jco.2020.38.15_suppl.3000
Immune system modulators for cancer therapy. National Cancer Institute. (n.d.). Retrieved February 19, 2022, from https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/immune-system-modulators
Monoclonal antibodies. National Cancer Institute. (n.d.). Retrieved February 17, 2022, from https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/monoclonal-antibodies
NCI Dictionary of Cancer terms. National Cancer Institute. (n.d.). Retrieved February 15, 2022, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biological-therapy
Using oncolytic viruses to treat cancer (2022). National Cancer Institute. Retrieved February 19, 2022, from https://www.cancer.gov/news-events/cancer-currents-blog/2018/oncolytic-viruses-to-treat-cancer#:~:text=%E2%80%9CThe%20oncolytic%20virus%20kills%20tumor,the%20approval%20of%20T%2DVEC.