From Arthritis to Zoster

Immunotherapeutics are pharmacologic agents that modify immune mechanisms in order to treat disease. The list of immunotherapeutic agents is long and growing. Indeed, as researchers begin to recognize the roles that inflammation and other immune responses play in the evolution of various illnesses, a scientific discipline is blossoming around the development of new immunotherapeutic drugs.

Major Classes of Immunotherapeutics

A better understanding of immunotherapeutics and their actions can be gained by classifying these drugs into discrete divisions. While there is undoubtedly some overlap among these groups – for example, an agent that is classified as a soluble cytokine might also be a fusion protein – their categorization affords clearer comprehension:

Monoclonal Antibodies

A more thorough discussion of antibody production and function is found elsewhere. Simply put, antibodies are complex proteins that bind to antigens (foreign substances) and inactivate or destroy them. For every potential antigen that might prove troublesome to an organism, a specific antibody can be manufactured. Hence, antibodies can target disease-causing microbes, proteins, or parts of abnormal (or even normal) cells. This antigen-specific property makes antibodies an intriguing candidate for treating a host of diseases and conditions.

Unfortunately, the B cells that are responsible for producing a particular antibody only live for a short time; as they grow senescent, they are replaced by new B cells. So, even if scientists could place a B cell in a test tube and provoke it to make a specific antibody, that cell would only produce those antibodies for a limited period of time before it died.

Therefore, in order for antibodies to be useful therapeutic agents for a significant number of individuals, they must be manufactured in large amounts, they must be of a very specific type (i.e., all coming from an identical, or monoclonal, line of B cells), and the ability to produce them must be “immortalized.”

The technology surrounding monoclonal antibody production has been evolving since 1975, when Köhler and Milstein developed antibody cloning methods for mice. These methodologies have since been extended to humans, and a plethora of monoclonal antibodies are available for treating conditions ranging from rheumatoid arthritis and other autoimmune diseases to various cancers and post-operative states (e.g., prevention of restenosis in patients undergoing angioplasty).

Fusion Proteins       

The useful properties of two or more proteins can be combined by joining the genes that encode for the proteins. In this way, desirable attributes of the parent molecules can be had in a single, chimeric protein.

For example, it is possible to produce a conjoined molecule that contains an antibody to a receptor found on a cancer cell along with a toxic agent that kills the cancer. When such a molecule is administered to a patient who suffers from that specific cancer, the antibodies seek out the cancer cells and deliver a targeted dose of chemotherapy. This affords more effective therapy while lessening the burden of side effects.

Fusion proteins are being used to treat severe psoriasis, rheumatoid arthritis, and certain lymphomas.

Cytokines

Cytokines are messenger molecules that modulate a vast array of immunologic responses. They are released (and interpreted) by lymphocytes, neutrophils, and other immune cells.  The activities of cytokines can be used to advantage in a number of conditions, including immunodeficiency states, cancer, multiple sclerosis, certain viral infections (e.g., hepatitis C), and to stimulate the immune system following chemotherapy.

Soluble Cytokine Receptors 

When cytokines induce abnormal levels of inflammation or encourage the growth of malignant cells (that is, when cytokines “go bad”), blocking these cytokines’ actions often ameliorates the disease process.

Soluble cytokine receptors are designed to block the activity of undesirable cytokines. Some of these receptors may competitively attach to cellular sites, thus preventing the binding of cytokines to those cells; others may bind to the cytokines themselves to prevent cellular signaling.

Soluble cytokine receptors are used in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, allergic disorders, and some forms of cancer.

Several dozen immunotherapeutic agents are currently on the market in the U.S. Since this is one of the fastest-growing technologies in health care – researchers are finally acknowledging the importance of immune activity in the genesis of disease, as well as its prevention and treatment – the roster of effective immunotherapeutics is expanding rapidly.