Wistar and Penn Medicine Receive $ 11.7 Million Melanoma Research Grant from National Cancer Institute

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Newswise – PHILADELPHIA – (September 22, 2021) –The Wistar Institute and Penn Medicine received a prestigious $ 11.7 million Specialized Research Excellence Program, or SPORE, grant from the National Cancer Institute. The five-year award will fund three new melanoma research projects that translate fundamental laboratory findings from the Wistar Institute and the Perelman School of Medicine at the University of Pennsylvania into new therapies to treat skin cancers.

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.

The Wistar and Penn SPORE team will continue a long tradition of developing new treatments for skin cancer through the grant, which follows a SPORE grant of $ 12 million awarded to establishments in 2014. The new projects will be supported by basic research laboratories, including a core of tissue specimens containing over 11,000 specimens in the bank.

Meenhard Herlyn, DVM, D.Sc., Director of the Wistar Melanoma Research Center and Professor in the Molecular and Cellular Oncogenesis Program at the Wistar Cancer Center, and 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 Penn’s Abramson Cancer Center, and will be Co-Director of SPORE.

“Despite the dramatic improvement in immunotherapy, we still have major challenges for the majority of patients and new approaches are urgently needed,” Herlyn said. “Building 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. “

“Our 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, ”said Amaravadi. “From 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. “

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 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. .

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.

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 finding that small segments of cells called exosomes that carry PD-L1 on their surface float in the blood of patients with melanoma. Exosomal PD-L1 is an immunosuppressive factor and can be measured in the 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

Currently, 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.

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The Wistar Institute is an international leader in biomedical research with particular expertise in cancer research and vaccine development. Founded in 1892 as the first independent, not-for-profit biomedical research institute in the United States, Wistar has held the prestigious designation of Cancer Center from the National Cancer Institute since 1972. The institute works actively to ensure that advances in research moves from the lab to the clinic as quickly as possible. wistar.org.


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