Given their central role in controlling immunity, dendritic cells are logical targets for many clinical situations that involve T cells. New therapies are being developed to use dendritic cells not only to produce vaccines that prevent infection but also to create immunotherapies that bolster attacks on pathogens and cancers, encourage the tolerance of transplanted tissues, and short-circuit autoimmune disease.

During early research on dendritic cells, several laboratories administered antigens to experimental animals and identified the cells that had captured them in an immunogenic form. Regardless of the route of antigen administration (blood, muscle, skin, intestine, or airway), dendritic cells were the major reservoir for producing the immunogens to T cells.

The next experiments in Steinman's laboratory involved removing dendritic cells from animals, exposing them to antigens outside the body, then re-injecting them into immunologically naive recipients. The result was that dendritic cells primed an animal's T cells directly, in the absence of any other adjuvants. In other words, dendritic cells immunized the animals, a fact that has led to their description as "nature's adjuvants."

These experiments raised the exciting possibility that scientists could use dendritic cells to vaccinate against tumors, infections, and transplants in patients. Previous vaccines have provided "passive immunization" in which an individual receives a large number of cells that are activated prior to injection. These vaccines provide immune cells whose life span, diversity, and efficacy are limited.

In contrast, dendritic cell based immunization is a completely new form of immune therapy in which small numbers of antigen-charged dendritic cells produce "active immunization." In this therapy, individuals make their own diverse and longer lasting immune response to the dendritic cells.

Several laboratories are initiating clinical studies to prove the principle of this therapy against cancers as diverse as melanoma, lymphoma, and tumors of the prostate and colon. This new form of immune therapy begins with the isolation of dendritic cell precursors from the patient, usually from blood. These precursors develop in the laboratory (in simple tissue culture systems) into large numbers of more mature dendritic cells. During this time, the dendritic cells are charged with antigens from the patient's tumor or infection. Then the dendritic cells are reinfused in the patient to elicit immunity and thereby resistance to the disease.

Another therapeutic approach under study is to find ways to turn off the activity of dendritic cells in situations where they exacerbate instead of fight disease. For example, dendritic cells provide a safe haven for several viruses, including HIV-1 and measles. The dendritic cells pick up viruses and become infected with them as they prowl the mucous membranes and travel to lymph nodes and deliver the virus to the large concentration of T cells. Rather than battling the infection, the mature dendritic cells assist in transmitting and spreading it. One potential treatment might be to prevent the virus from first binding to its special site on immature dendritic cells, thus precluding their maturation and migration to the lymph nodes.

These approaches are still in preliminary stages. Tailoring a dendritic cell vaccine to fight a particular patient's tumor is costly and time-consuming. Therefore, many scientists are also working to prompt dendritic cell precursors already present in a person's body to divide and start an immune response against their tumors. Many unknowns remain in dendritic cell biology: finding optimal antigens, targeting the most effective stage in the cell's life cycle, delivering antigens to their correct destination.