Prostate cancer is still the most common non-skin cancer in American men, affecting one in every six males. Two University of Iowa researchers received an exploratory grant to develop an enhanced vaccine to treat and prevent prostate cancer. Aliasger Salem, PhD, assistant professor at The University of Iowa College of Pharmacy and one of the two researchers working on the vaccine, talks about the grant:
Is there currently a vaccine to protect men against prostate cancer?
There are a number of promising prostate cancer vaccines are currently in development. Some of these prostate cancer vaccines are listed at the National Institutes of Health (NIH) clinical trials. These include GVAX® Vaccine for Prostate Cancer by Cell Genesys, Inc. Another potential vaccine is Provenge® that is being developed by the NIH. Another potential vaccine that is showing a lot of promise is an adenovirus based vaccine encoding prostate-specific antigens that is currently being tested in clinical trials by David Lubaroff, PhD.
GVAX® is based on cells from two, patient-non-specific prostate cancer cell lines that have been genetically engineered to overexpress and secrete GM-CSF, which stimulates the immune response to vaccines. Provenge® aims to use the patient's own immune system cells trained in the laboratory to target the protein prostatic acid phosphatase (PAP), which is made by prostate cells.
Have studies been done in the past to develop a vaccine to prevent or treat prostate cancer?
Lubaroff’s lab has been studying a prostate cancer vaccine for over 10 years. His studies have focused on the utilization of an adenovirus encoding PSA. PSA is Prostate Specific Antigen and it is a prostate-specific protein antigen that can be found circulating in the blood, as well as on prostate cancer cells. PSA is generally present in small amounts in men who do not have cancer, but the quantity of PSA generally rises when prostate cancer develops. The higher a man's PSA level, the more likely it is that cancer is present.
What is different about the approach you and your colleagues will be using to develop this enhanced vaccine?
With PSA being an ideal target antigen for immunotherapy because it has a narrow distribution in tissues and is expressed in virtually all prostate cancers, we are looking to combine non-viral gene delivery techniques and viral gene delivery techniques to stimulate the most potent anti-tumor antigen-specific immune response to date.
Gene delivery techniques have the potential to stimulate potent anti-tumor immunity and studies to date have focused either on non-viral delivery systems such as plasmid DNA-polycation complex co-acervates or nanoparticles, or viral approaches such as the adenoviruses encoding prostate specific antigen (PSA). Non-viral plasmid DNA sequences contain CpG motifs.
Our groups have shown that CpG motifs enhance the efficacy of Ad5-PSA vaccines tumor protection. Our groups have also shown that CpG ODN delivered in particulate form is significantly more potent than delivery in solution. Chitosan is a safe natural polymer that complexes with plasmid DNA (with CpG motifs) to form non-viral gene delivery nanoparticles. The objective of our experiments is to test the idea that co-delivery of non-viral nanoparticles with adenoviruses will enhance tumor protection in a pre-clinical model of prostate cancer.
How many years will you work on this project?
We hope to work on this project for at least two years and beyond if funding allows.
Who is funding the research?
This is being funded through the National Cancer Institute at the National Institutes for Health.
What do you hope to determine with this pre-clinical research?
Primarily our objective is to develop a new therapeutic modality that can enhance the prevention and treatment of prostate cancer better than current treatments.
What will the next steps be after this initial pre-clinical research?
Once we have exhaustively characterized the vaccine, including pre-clinical studies evaluating potential toxicity, our next longer-term objective would be to carry out clinical trials. Ultimately, we hope that the results generated from these studies will act as a platform to translational applications in patients.
If all goes well, how long would it be before this vaccine you are developing might be used in a clinical situation?
We anticipate that it would take five to six years before this vaccine formulation can reach phase 1/phase 2 clinical trials--if all goes well.
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