A new type of immunotherapy in which dendritic cells are tricked into action against cancer when they are exposed to harmless pieces of viruses and bacteria is described in the November issue of Cancer Research.
Dendritic cells, the pacemakers of the immune system, are known to play a vital role in the initiation of the immune response but are often eluded by cancer.
In the study, University of Pittsburgh researchers describe the creation of an animal model of an immunotherapy approach that, first used in cancer patients, uses a patient's own tumor cells to stimulate anti-tumor immunity. The discovery of the animal model will enable researchers to more fully understand and develop the approach.
"Cancer cells are very adept at camouflaging themselves and hiding from the immune system and this makes most cancers, including melanomas and lymphomas of the skin, extremely challenging to treat with existing immunotherapies," said Louis D. Falo, M.D., Ph.D., professor and chairman of the department of dermatology at the University of Pittsburgh School of Medicine. "While we know that dendritic cells are necessary to activate a response against cancer as the first cells to present antigens to other cells of the immune system, they are often ineffective because they fail to recognize growing cancers as dangerous. What we describe is an immunotherapy approach that activates dendritic cells by using an external stimulus that mimics danger. This alerts the cells to activate a type of immune response that is particularly important for fighting cancer."
In the study, melanoma cells and dendritic cells from mice were removed, combined together in a culture dish and exposed to pieces of viruses and bacteria. The researchers used the most aggressive mouse melanoma tumor, B16, which has multiple mechanisms to escape the immune system that are similar to those used by human cancers. They found that the dendritic cells were able to extract antigens directly from tumor cells. By exposing the antigen-bearing dendritic cells to harmless pieces of bacteria and virsuses that they preceived as dangerous, the researchers "tricked" them into recognizing the tumor as dangerous as well. The alerted cells were then injected back into the mice where they successfully activated a particular T-cell response important for fighting tumors. That response, called Th1, led to a significant reduction in tumor growth in the mice.
"Typically, tumors are able to grow in part by convincing the immune system that they are normal. Our goal was to mimic danger to wake up the dendritic cells and program them to stimulate the right type of immune response against the patients' own tumor cells," said Dr. Falo.