Modified Dendritic Cells Induce Immune Response

PITTSBURGH—University of Pittsburgh researchers have shown that immature dendritic cells can be genetically modified to serve as an effective vehicle for presenting tumor antigens to the immune system. Such cells were shown to induce a significant and therapeutic tumor-specific immune response in an animal model.

The finding resulted from a two-step investigation, Hideaki Tahara, MD, PhD, assistant professor of surgery, reported at the 90th annual meeting of the American Association for Cancer Research (AACR) in Philadelphia.

First, the dendritic cells, a type of antigen-presenting cell, were injected directly into tumor tissue in mice. Then, Dr. Tahara and his colleagues studied the animals’ spleen and lymph nodes to measure the systemic immune response.

They found that the injected dendritic cells were able to process the tumor antigens at the tumor site, migrate to the lymph nodes, and present the antigens to the lymphoid cells, which released significant quantities of interferon-gamma, an immunostimulatory substance. “Interferon-gamma levels were significantly higher in these mice than in animals that received saline,” Dr. Tahara said.

In the second step, Dr. Tahara’s group genetically modified immature dendritic cells to secrete the tumor-fighting and immunostimulatory substance interleu-kin-12 (IL-12), and injected the cells directly into tumor tissue. The secretion of IL-12 by the genetically modified dendritic cells was found to further enhance the immune system’s response to the tumor.

“We have developed a system that is able to effectively present the tumor as a foreign agent to the immune system and simultaneously activate the immune system’s response to the tumor,” Dr. Tahara said, “and we are now moving forward with studying this system in cancer patients.”