What is tumor necrosis factor (TNF)?

Cancers treated: Breast cancers, ovarian cancers, colon cancers, kidney cancers, 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 an injection in a vein or muscle. Injection may also be 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 ability of the drug to bind normal tissue and possibly permitting systemic delivery.

How this drug works: The term TNF actually 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 and is induced in the presence of 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. Binding of TNF sets in motion a series of intracellular signals that results in the death of the cell.

Testing has also been carried out using a human recombinant form of TNF (rTNF), as well as treatments utilizing a combination of chemotherapies in conjunction with TNF.

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 the course of 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 also can contribute to other diseases including autoimmune disorders.

Bibliography

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