PITTSBURGHUniversity 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
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. Taharas 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 systems 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 systems response to the tumor, Dr.
Tahara said, and we are now moving forward with studying this
system in cancer patients.