11/12/2013

The University of Pittsburgh Cancer Institute (UPCI) Melanoma and Skin Cancer Program (MSCP) led by John Kirkwood, M.D., has received renewal of its skin cancer research through the National Cancer Institute’s competitive Specialized Program of Research Excellence (SPORE) program. The grant is for more than $12 million.

The award is the fourth grant awarded to UPCI through the prestigious SPORE program, which requires cancer institutes to document strong collaboration between eminent scientists and clinicians as well as outstanding programs in translational research. The other three grants at UPCI are in head and neck, lung and ovarian cancers.

The SPORE grant for skin cancer will fund three new projects and the expansion of one prior project. These include: 

• Biomarkers of the proinflammatory response and elements of immune suppression: The goal of this project is to find biomarkers in melanoma patients at diagnosis or early in the disease that may predict the benefit of treatment with the drugs ipilimumab or interferon-α (IFNα) for each individual, as well as to assess the risk of melanoma recurrence and death. This effort continues earlier research that revealed biomarker patterns associated with pro-inflammatory immune responses and with immunosuppression in both tumor tissue and circulating blood.
• Multiple antigen-engineered dendritic cell immunization and IFNα-2b boost for vaccine immunotherapy of metastatic melanoma: This project tests an improved dendritic cell vaccine targeting tumor antigens given in combination with IFNα-2b with the aim of boosting the immune response against the cancer.
• Safety and efficacy of vemurafenib and high-dose IFNα-2b for advanced melanoma: This project will test whether vemurafenib, a drug that inhibits a signaling protein called BRAF, can enhance the therapeutic efficacy of IFNα-2b in patients with metastatic melanoma. In earlier work, the team found BRAF inhibitors make melanoma cells more sensitive to the effects of IFN-α, suppressing cell proliferation and encouraging apoptosis, or programmed cell death; increase T cell-mediated immune responses to melanoma cells; and prolong the survival of mice in a model of melanoma.
• A microneedle vaccine program for immunotherapy of melanoma and cutaneous T cell lymphoma

Dr. Kirkwood’s melanoma research team first received SPORE funding five years ago and the grant’s five past projects have focused on immune approaches to treatment of melanoma and other skin cancers. The incidence of melanoma continues to rise dramatically. There has not been effective therapy to improve overall survival for the majority of patients with inoperable metastatic disease, although progress in the molecular therapy and immunotherapy of melanoma now has improved prospects for patients with melanoma considerably.

“We want to improve our understanding of the molecular and immunologic mechanisms underlying melanoma progression and to validate prognostic and predictive biomarkers that will lead to the personalized treatment of melanoma and other skin cancers,” Dr. Kirkwood said. “Our research is unique because we have integrated an approach that includes experts in melanoma from medical oncology, dermatology, surgery, immunology, biostatistics, bioinformatics, and biomarker discovery.”

Nancy E. Davidson, M.D., director of UPCI and its clinical partner, UPMC CancerCenter, called the SPORE grant a “perfect storm” in that it combines UPCI’s long-term scientific and clinical expertise in melanoma and immunology with the activities of the Department of Dermatology under the leadership of Louis Falo, M.D., Ph.D., and is tightly linked to national and international clinical trials activities in the cooperative groups.

“Multidisciplinary care is at the crux of modern cancer medicine and is critical for scientific discovery and translation,” Dr. Davidson said. “This SPORE grant is a great example of that.”

About 76,000 new cases of melanoma are diagnosed every year in the United States and about 9,400 people will die every year from the disease, according to the National Cancer Institute.

Dr. Kirkwood said the work being done through the SPORE grants is already making a difference. There have been several new therapies for melanoma approved since 2011, compared to just three agents approved in the 30 years prior.