Excitement tempered by long road ahead for dendritic cell vaccines.

Cancer vaccines based on dendritic cells—the immune system's first responders to foreign invaders— grabbed the spotlight this summer. Several vaccines showed remarkable responses in early clinical trials in patients with advanced tumors, and in one animal study, a dendritic cell vaccine wiped out tumors in mice with melanoma. At this point, it is anybody's guess which, if any, of several approaches to vaccination using dendritic cells will make a difference for cancer patients. The scientists who are doing the work mix terms like " cautious optimism " and " potentially promising " with " uphill battle " and " suboptimal process. " " We're learning how to find tumor antigens, how to make more effective vaccines and make them more potent, and how to block or turn off negative regulatory mechanisms of tumors, " said chief of the Vaccine Branch at the National Cancer Institute. " Dendritic cells are clearly the most important modulator of immune responses in the body, " said David E. Avigan, M.D., director of bone marrow transplantation at Beth Israel Deaconess Medical Center in Boston. They roam the circulatory system to collect foreign invaders or other antigens and carry them to the lymph nodes, where they present them to the T cells. This primes the T cells to mount an attack against those antigens. Cancer cells have found ways to evade the immune system, but specially programming a patient's own dendritic cells may be one way to unmask the tumor and alert the body to mount a strong defense. During the past decade, scientists have devised a dozen different ways to make dendritic cell vaccines. They have linked dendritic cells with all kinds of antigens, including peptides derived from gene mutations, tumor RNA, viral vectors, and with whole tumors. And they are adding cytokines such as granulocyte–macroph-age colony-stimulating factor (GM-CSF) or interleukin 4 during dendritic cell growth or maturation or at the site of vaccination to try to boost response. " We're still learning the best way to make the dendritic cells, send them to the right place in the body, and use the biological stage of development that is most suited to stimulate a response, " Avigan explained.