Tumor necrosis factor (TNF)
Tumor necrosis factor (TNF) is a cytokine, a type of immunoregulatory protein produced primarily by white blood cells in response to infections or antigens. Its primary forms, TNF-alpha (TNF-α) and TNF-beta (TNF-β), have garnered interest in the field of cancer therapy due to their ability to induce cell death in certain tumor cells. This mechanism involves attacking blood vessels in tumors, leading to tumor regression through a process known as apoptosis, or "cell suicide." While TNF has shown promise in treating various cancers, including breast, ovarian, and liver cancers, its effects can be both beneficial and harmful, necessitating further research into its use. The administration of TNF typically occurs through injections, and innovative approaches like colloidal formulations aim to enhance specificity for cancer tissues. However, TNF treatment can lead to side effects, including mild fever and fatigue, and may interact with other medical treatments. Additionally, TNF's role is complex, as it can also contribute to cancer proliferation and other autoimmune disorders, leading to exploration of TNF inhibitors in treating conditions like rheumatoid arthritis. Overall, while TNF holds potential in immunotherapy, its dual nature underscores the importance of careful study and application.
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Tumor necrosis factor (TNF)
DEFINITION: TNF is a protein belonging to the class of cytokines (immunoregulatory proteins) that is made by the body’s white blood cells in response to an infection or antigen. It can also be synthesized in the laboratory. Because it causes necrosis (cell death), it has been investigated as a possible immunotherapeutic drug to induce the death of some types of tumor cells. However, due to TNF having both beneficial and detrimental effects regarding immunotherapy, increased study remained necessary.
ALSO KNOWN AS: Tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-beta (TNF-β, or lymphotoxin); the colloidal gold-bound form of TNF is also called Aurimmune
Cancers treated: Breast cancers, ovarian cancers, colon cancers, kidney cancers, soft-tissue sarcomas, and liver cancers, as well as melanomas; tests carried out with a variety of other tumors
Delivery routes: Tumor necrosis factor is generally delivered as a vein or muscle injection. It may also be injected under the skin. A colloidal form of TNF bound to small particles of gold has also been tested for improved specificity for cancer tissue, reducing the drug's ability to bind normal tissue and possibly permitting systemic delivery.
How this drug works: The term TNF refers to a family of trimeric proteins produced by certain types of white blood cells that can attack blood vessels in tumors, thereby destroying certain types of cancer cells. The most common forms are TNF-α and TNF-β. TNF-α is the form used for cancer therapy. Its existence was discovered fortuitously in the early twentieth century, when physicians observed that certain types of tumors would spontaneously regress in the presence of bacterial infections. It was subsequently discovered that TNF production is a part of the immune response induced by bacterial endotoxin (lipopolysaccharide).
The response to TNF is dose-dependent and can result either in inflammation, augmenting the immune response, or in binding to a cell surface, inducing the destruction of that cell. The induction of apoptosis, or “cell suicide,” appears to be the primary mechanism by which TNF may cause tumor regression. Depending upon the state of the particular cell, either tumor cells or the cells of the blood vessels that feed those tumors may express receptors on their respective surfaces for the drug. The binding of TNF sets in motion a series of intracellular signals that result in the cell death.
Testing has also been carried out using a human recombinant form of TNF (rTNF) and treatments utilizing a combination of chemotherapies and TNF. Further, the advent of targeted therapies has allowed for a more individualized approach to TNF treatments.
Side effects: Like other forms of chemotherapy, TNF has the potential to interact with other medications. Since TNF may interact with other cells of the immune system, vaccinations should be avoided during treatment. Specific side effects of TNF may include a mild fever, chills or sweating, fatigue, and vomiting. Since most cells in the body have surface receptors to which TNF may bind, the drug is potentially toxic if given systemically. Despite its potential as an anticancer agent, TNF has also been investigated for its possible role in cancer proliferation. It can also contribute to other diseases, including autoimmune disorders; therefore, successful studies in the use of TNF inhibitors as effective treatment for autoimmune diseases such as rheumatoid arthritis have also been conducted.
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