Clec9A Targeting Antibodies as a New Immunotherapy for Prostate Cancer
Abstract
Scientific Objective and Rationale: It is now well recognized that a patient s own immune system can be harnessed to recognize and fight cancer. This type of treatment, called cancer immunotherapy, was named by Science magazine as "Breakthrough of the Year" in 2013 for being one of the most significant advances in cancer treatment in recent times. For metastatic prostate cancer, there is now a Food and Drug Administration-approved vaccine treatment (Sipuleucil-T, Dendreon) that significantly improves survival, demonstrating that this disease is one for which immunotherapy will be particularly beneficial. Special white blood cells called dendritic cells can teach the body s own immune response to fight cancer and are the key component of therapeutic cancer vaccines. We have made several key discoveries that have the potential to significantly improve the effectiveness of cancer vaccines. First, we have discovered that there are many different types of dendritic cells and have identified the subtype now considered to be the most effective at mounting anti-cancer immune responses in humans. Second, we have developed a novel antibody specific for the "cancer-fighting" dendritic cells that can be used to deliver the vaccine directly to them. In this project, we will construct a new vaccine for metastatic prostate cancer and test its efficacy using novel laboratory assays we have developed specifically to test human vaccines. Ultimate Applicability of Research: Our strategy would be to develop the vaccine initially as a treatment for metastatic prostate cancer patients. This is because the currently approved treatments for this disease offer at best a maximum survival advantage of only 5 months and therefore new treatments are urgently required. As one of only a handful of new treatments approved in the past decade for metastatic prostate cancer that has been demonstrated to significantly improve patient survival, vaccines for prostate cancer warrant further development. The major outcomes of this project at the end of 3 years will be to establish that construction of this type of vaccine is feasible and to provide evidence in human cells that this vaccine can induce anti-cancer immune responses. This would provide the mandatory preclinical data that would justify testing this vaccine in a Phase I clinical trial. Our vaccine has been designed so that it can be seamlessly transferred into the clinic in a minimal time frame should it be successful. Over 15 years of clinical trials using dendritic cell vaccines have taught us that in addition to inducing anti-cancer immune responses, these vaccines are very safe to administer and are devoid of the toxic side effects associated with many other therapies. Moreover, they have great potential to be used in combination with other treatments to synergize anti-cancer effects and minimize toxicity. If successful, our vaccine may also be suitable for treating earlier stage prostate cancer patients and also other malignancies including ovarian cancer and melanoma. Likely Contributions to Advancing the Field: Although there is clear evidence that cancer vaccines can induce immune responses and be effective in some patients, overall the responses have not yet lived up to expectations and there is a clear need for improvement. Our project will significantly advance the field by developing a novel approach to specifically deliver the vaccine to the cell type considered most effective at inducing anti-tumor immune responses. To date, there are no vaccine strategies with this level of specificity or that don t require patient s blood for manufacture, a procedure that is expensive, impractical, and not suitable for many patients or widespread use. Thus, a vaccine that overcomes these limitations in addition to the likelihood of being more efficacious with less side effects due to the highly specific targeting nature will be highly significant to the field.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510451
Entities
People
- Kristen J Radford
Organizations
- United States Army
- University of Queensland