A new study suggests that antibody-based cancer drugs might help patients more if they are given with substances that stimulate the immune system.
This new study is the first to indicate that the drug trastuzumab, also known as Herceptin, may work better when it is followed by injections of interleukin (IL) 2 or IL-12. Both substances trigger the activity of immune cells known as natural killer (NK) cells.
The research, by scientists at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, is published in the Jan. 1 issue of the journal Cancer Research.
The drug trastuzumab consists of an antibody that targets the protein HER2, which is present on cancer cells of many breast tumors. NK cells are the body's first line of defense against many infections, and they also attack tumor cells.
NK cells rush into action when they encounter bacteria or other foreign agents in the body that are coated with antibodies, large proteins released by immune cells in response to the presence of foreign material in the body.
Trastuzumab is used to treat advanced breast cancer cases that over-produce the HER2 protein. The drug coats the tumor cells with antibodies, but it is unclear exactly what happens next.
Presently, researchers believe that when the trastuzumab antibodies join with the HER2 protein, they trigger changes within the tumor cells that cause the cells to die or to grow more slowly. In this scenario, the immune system plays a relatively minor role in slowing the tumor's growth.
"But our results show that the immune system really can play an important role in this therapy and that the outcome of patients treated with antibody-based drugs might be improved by activating the patient's immune system with agents such as IL-12," says principal investigator William E. Carson, III, associate professor of surgery and director for clinical research at the OSU Comprehensive Cancer Center.
First author Julie M. Roda, a graduate research associate in Carson 's laboratory, explained why this is so.
"The findings suggest that using trastuzumab and the IL-12 together makes the body think an infection is under way, and this activates cells of the immune system to eliminate tumor cells in the same way they would eliminate an infection," says Roda.
The investigators found that the combination of antibody-coated cells and IL-2 or IL-12 causes the NK cells to release substances that attract more potent immune cells – mainly killer T cells – thereby trigging a larger and more effective immune response against the tumor.