Immune cells primed for cancer vaccine.

Patrolling the body's tissues, dendritic cells are watchdogs for the immune system. If interlopers-bacteria or viruses, for example-roam through the body, dendritic cells help alert the rest of the immune system to the invasion.

Investigators inspired by the idea of vaccinating people against cancer are now turning their attention to these cells. In the first study of its kind in humans, injections of specially treated dendritic cells have eliminated the tumors in one patient with non-Hodgkin's lymphoma and have aroused immune responses against the tumors in three other patients with the same cancer.

"These responses have been very strong and intense," says Frank J. Hsu of Stanford University. Hsu and his colleagues, including Ronald Levy and Edgar G. Engelman, report their results in the January Nature Medicine.

One of the guiding principles behind cancer immunotherapy is that cancer cells sport tumor antigens-proteins or other surface molecules that distinguish these cells from healthy cells. Consequently, cancer vaccine developers wish to coax the immune system into killing cells that display these antigens.

To do this, many investigators have injected tumor antigens directly into the bloodstreams of patients, either alone or with compounds designed to elicit a stronger immune response. Dendritic cells would be expected to gobble up these antigens and then display the molecules on their surfaces, thereby telling other immune cells what targets to destroy. But, says Hsu, simple injections of these antigens do not provoke antitumor immune responses in every patient, and the responses that do occur range widely in intensity

To eliminate this frustrating inconsistency, the investigators primed the dendritic cells with a unique tumor antigen from the cancer cells of each patient. They harvested young dendritic cells from a patient, grew them in a solution that contained large amounts of that patient's tumor antigen, and reinfused the cells into the patient.

This, they believed, would guarantee that the dendritic cells present the antigen properly. To further increase the antitumor response, the investigators also followed each cellular treatment with injections of the tumor antigen.

"We think it's a stronger, more potent way of immunizing people," says Hsu, who cautions that the new approach needs refining. Although the vaccine generated immune cells that specifically recognized tumor cells in all four patients, only in one was the response strong enough to cause complete remission.

Other investigators are now testing primed dendritic cells in animals with a variety of cancers, says Hsu. They also plan to treat people with melanoma, a cancer for which there is an identified tumor antigen (SN: 12/14/91, p. 388).

"It's an interesting approach, but it's just one of many ways of immunizing people that we're exploring. It's very difficult to predict which approach will work in humans," says Steven A. Rosenberg of the National Cancer Institute in Bethesda, Md.