Douglas McNeel, MD, PhD, professor, Hematology, Medical Oncology and Palliative Care, has been awarded $1.1M over three years from the Department of Defense (Prostate Cancer Research Program, Impact Award) for a proposal entitled “Targeting B Cells as Antigen-Presenting Cells for Improved Anti-Prostate Cancer DNA Vaccines.”

Researchers with Dr. McNeel's laboratory and a spinoff company he founded are developing vaccines that that train the immune system to recognize prostate cancer cells that express particular proteins. To do this, they are using DNA vaccine technology. 

With this approach, DNA is injected (or otherwise delivered) that encodes the antigen(s) against which an immune response is sought. DNA vaccines are an alternative to cell-based cancer immunotherapies such as one called sipuleucel-T approved by the FDA in 2010, which are much more costly to produce - resulting in treatment costs of over $100,000 per year. 

However, while work by Dr. McNeel's group has conducted studies on the safety of prostate cancer DNA vaccines in animal studies and early human clinical trials, they have also been less immunologically potent than other kinds of vaccines. Other scientists studying DNA vaccines for various purposes have reported similar findings. Thus, Dr. McNeel's team has been working on ways to increase the immunogenicity of prostate cancer DNA vaccines. 

When Dr. McNeel's team investigated what happens when different cells of the immune system take up DNA vaccines, the results were unexpected. Dendritic cells, which normally function to present antigens to the T cells of the immune system, turned out to be poor harbingers. "We found, surprisingly, that most of the DNA taken up directly by these cells is degraded," wrote Dr. McNeel. 

However, B cells - which are usually thought of as being dedicated to producing antibodies, not with starting immune responses - turned out to be much more amenable. "We then found that if we deliver DNA to B cells, and deliver these B cells as a vaccine, that we generate a more potent immune response than by just delivering DNA as is typically done with vaccination.  These findings suggest that the general approach of DNA immunization could be greatly improved by targeting B cells, and this is the focus of this [research]," he wrote.

The three-year research project will involve mouse and human clinical studies to further evaluate how best to deliver prostate cancer DNA vaccines to B cells. By the end of the project, scientists hope to have a workable strategy to take into clinical trials.

Resources:

• "Immunotherapy: Harnessing Cellular Systems to Fight Deadly Diseases," UW School of Medicine and Public Health, January 2, 2017