2010 Research Awards » Established Investigator Awards
MRA awarded two investigators who have committed their research careers to oncology and are pursuing novel ideas in melanoma research.
Multipeptide vaccination with or without IL-12 and Daclizumab
Thomas Gajewski, M.D., Ph.D.,
The University of Chicago
Melanoma vaccines offer an opportunity for instructing the immune system to selectively kill melanoma cancer cells in patients, thus comprising a treatment with minimal side effects. Vaccines developed to date frequently induce activated T cells against tumor antigens, yet only a minority of melanoma patients have tumor regressions. Metastatic melanoma tumors often contain CD4+CD25+ FoxP3+ regulatory T cells (Tregs), which have been shown to suppress the immune response that is induced. We propose that depleting such Tregs from patients will relieve this suppression and thus improve efficacy of melanoma vaccines in patients. The overall goal of this proposal is to test two strategies for vaccination, then deplete Tregs using a monoclonal antibody called Daclizumab. This study also will probe the tumor microenvironment in search for molecular details of the tumor that predict clinical benefit with this treatment.
Entrapment and deletion of melanoma-specific T cells at vaccination sites
Willem W. Overwijk, Ph.D.,
University of Texas M.D. Anderson Cancer Center
While cancer vaccines can stimulate the body’s defenses to fight cancer, this stimulation often isn’t strong enough to cause complete cure. Recently, vaccination with a mineral oil-based vaccine increased the lifespan of patients with metastatic melanoma undergoing standard therapy. Much room for improvement remains, and we here show results that suggest inherent limitations to mineral oil-based melanoma vaccines. Specifically, we find that melanoma-specific killer cells travel to the vaccine injection site and not to the melanoma where they are needed to destroy tumor cells. In addition, the killer cells die at these vaccine injection sites. In this proposal we will investigate what causes killer cells to travel to vaccine injection sites rather than to melanoma tumors, and what causes them to die there. We will also develop new, water-based vaccines that we predict will not cause killer cells to traffic to vaccine sites and die. The findings from this proposal will directly result in new therapeutic anti-melanoma vaccines with superior anti-melanoma activity for the treatment of melanoma patients.