PHILADELPHIA CREAM – Penn medicine and The Wistar Institute received a prestigious $ 11.7 million grant from the Specialized Research Excellence Programs, or SPORE, from the National Cancer Institute. The five-year award will fund three new melanoma research projects that translate fundamental laboratory findings from the Perelman School of Medicine at the University of Pennsylvania and the Wistar Institute into new therapies to treat skin cancer.
The grant also includes a career enhancement program focused on training and retaining underrepresented minorities in skin cancer research, and a pilot reward program that will expand skin cancer research further. than melanoma.
Penn and Wistar’s SPORE team will continue a long tradition of developing new treatments for skin cancer through the grant, following a previous SPORE grant awarded to institutions in 2014. With considerable support from the Abramson Cancer Center (ACC) and the Tara Miller Melanoma Research Center, the team developed new expertise and resources, including a core of tissue samples with more of 11,000 samples banked, which helped secure the new SPORE grant.
Ravi K. Amaravadi, MD, Associate Professor of Hematology-Oncology at Penn’s Perelman School of Medicine and Co-Head of the Cancer Therapy Program at ACC, and Meenhard Herlyn, DMV, DSc, Director of the Wistar Melanoma Research Center and Professor in the Molecular and Cellular Oncogenesis Program at the Wistar Cancer Center, will be the co-directors of SPORE.
âOur long-standing team approach to science and new therapies has once again been recognized by NCI with this new SPORE grant. We can now extend this collaboration, which has already led to important developments in melanoma, âsaid Amaravadi. âFrom new foundational knowledge about how skin cancer escapes treatment to new treatment options for patients, these projects – and the people who lead them – are at the forefront of translational medicine and are entirely focused on l improving the health of our patients. ”
âDespite the dramatic improvement in immunotherapy, we still have major challenges for the majority of patients and new approaches are urgently needed,â Herlyn said. âBuilding on the major advances of our team, we are ready to answer critical unanswered questions to improve response to immunotherapy and identify new biomarkers to inform patient management and reduce therapy toxicity. ”
Melanoma is the deadliest form of skin cancer and the fifth deadliest form of cancer overall. According to NCI statistics, more than 100,000 new cases of melanoma will occur in 2021 in the United States alone. The incidence of melanoma and other skin cancers, such as Merkel cell carcinoma and squamous cell carcinoma, is increasing both nationally and regionally. If caught early, skin cancer is considered treatable; however, when these cancers metastasize, they are particularly fatal.
Other Penn professors involved in the project include Wei Guo, PhD, 1965 Class Endowed Biology Chair, Xiaowei Xu, MD, PhD, Professor of Pathology and Dermatology, Phyllis Gimotty, PhD, Professor of Biostatistics and Epidemiology, Giorgos Karakousis, MD, Associate Professor of Surgery, Gregory Beatty, MD, PhD, Associate Professor of Medicine, Tara Mitchell, MD, Associate Professor of Medicine, Lynn Schuchter, MD, Chief of Hematology-Oncology and director of the Tara Miller Melanoma Center, and E. John Wherry, chair of the systemic pharmacology and translational therapeutics department.
Other Wistar professors on the team include Professor David W. Speicher, Ph.D., Associate Professor Jessie Villanueva, Ph.D., and Assistant Professor Andrew Kossenkov, Ph.D., of the Wistar Institute Cancer Center. .
The three main SPORE melanoma research projects include:
Project 1: Exosomal PD-L1 in resistance to immunotherapy
Co-project managers: Guo, Xu, Mitchell and Wherry
Currently, there is no approved test that can help determine which melanoma patients will respond to immunotherapy. This project is based on a fundamental discovery that small segments of vesicles encapsulated in lipids released by cells called exosomes that carry PD-L1 on their surface float and circulate in the blood of patients with melanoma. Exosomal PD-L1 is an immunosuppressive factor and can be measured in blood non-invasively using the assay developed by Guo and Xu. In collaboration with collaborators from the John Wayne Cancer Institute, MD Anderson Cancer Center and New York University, the team will conduct rigorous clinical utility studies designed to demonstrate this blood-based measure as a predictive biomarker. highly sensitive and specific for the response to immunotherapy in melanoma.
Project 2: Targeting autophagy to improve immunotherapy in melanoma
Co-project managers: Amaravadi and Speicher
There are limited options for patients whose tumors have progressed on immunotherapy to melanoma. Based on extensive preclinical data and a new molecular target in the autophagy pathway, the team developed a clinical trial of combined immunotherapy and autophagy inhibition. Targeting autophagy during immunotherapy can reprogram cells within the tumor to improve the efficiency of T cell destruction of melanoma cells. This clinical trial will include a new PET imaging tracer capable of tracking T cells as they enter patients’ tumors. The project is also working with several biotechnology companies developing new inhibitors of autophagy for cancer.
Project 3: Neoadjuvant immunotherapy of early-stage melanoma
Co-project managers: Beatty, Karakousis and Herlyn
Currently, patients with stage III melanoma are treated with immunotherapy after surgical resection. Some patients with stage II melanoma have a higher risk of metastasis than patients with stage III, but there is no approved treatment to reduce this risk. Based on previous work showing that a cycle of immunotherapy given before surgery can produce major benefits in patients with stage III melanoma, the team initiated a clinical trial of neoadjuvant immunotherapy in patients with stage IIB / C melanoma. In addition to the in-depth characterization of the immune response, the project’s preclinical studies, which include several innovative mouse models to study immunotherapy in stage II melanoma, will lead to new strategies to improve the immune stimulating capacity of dendritic cells in the body. tumor microenvironment.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research and excellence in patient care. Penn Medicine consists of Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the country’s first medical school) and the University of Pennsylvania Health System, which together form an $ 8.9 billion company.
The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to the US News & World Report survey of research-driven medical schools. The school is consistently among the top recipients of funding from the National Institutes of Health, with $ 496 million awarded in fiscal year 2020.
Patient care facilities in the University of Pennsylvania Health System include: University of Pennsylvania Hospital and Penn Presbyterian Medical Center, recognized as one of the nation’s top hospitals by US News & World Report: Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the country’s first hospital, founded in 1751. Other facilities and businesses include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is fueled by a talented and dedicated workforce of over 44,000 people. The organization has also forged alliances with top community health systems in southeastern Pennsylvania and southern New Jersey, creating more options for patients no matter where they live.
Penn Medicine is committed to improving lives and health through a variety of community programs and activities. In fiscal 2020, Penn Medicine provided over $ 563 million to benefit our community.