In this translational research project, we have utilized the broad and significant expertise of multiple medical and scientific disciplines within the intramural and extramural community. Patients with metastatic uveal melanoma have been recruited directly to the CCR/NIH or via tertiary care collaborators at Memorial Sloan Kettering (MSKCC) or the University of Miami (U of Miami). Liver resection of uveal melanoma metastases have been performed by Dr. Kammula (Project Lead, Surgery Branch/NCI). Tumor DNA has undergone whole exomic sequencing by the SAIC-Frederick core facility. Dr. Stahlberg's team (CCR Informatics Core) has performed analyses to mine the sequence data for unique driver mutations expressed in the tumor. Dr. Raffeld (Laboratory of Pathology) has validated the mutational screen by independent next generation mutation analyses. In a future planned effort, multi-discipline consultation regarding patient suitability and choice of target mutations will be provided by Drs. Harbour and Acquavella (U of Miami) and Dr. Carvajal (MSKCC) who are experts in the mutational genomics and clinical care of uveal melanoma patients. Efforts to isolate mutation specific T cells have begun in Dr. Kammula's laboratory using novel high throughput GMP cloning techniques developed by his team. In an ongoing clinical trial (NCI13-C-0093), patients have been treated with bulk tumor infiltrating lymphocytes. These studies will be informative in defining the immune response to mutated antigens. In a planned future clinical trial, isolated mutation specific T cells will be administered back into the host patient using an adoptive immunotherapy platform established in the Immunotherapy section, Surgery Branch/NCI. Dr. Kammula will be the principle investigator on this clinical trial based in the CCR, NIH.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
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Basic Sciences
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Rothermel, Luke D; Sabesan, Arvind C; Stephens, Daniel J et al. (2016) Identification of an Immunogenic Subset of Metastatic Uveal Melanoma. Clin Cancer Res 22:2237-49
Bartlett, Edmund K; Kammula, Udai S (2014) Location, location, location: The relationship of anatomic site, antigen expression, and T-cell infiltration in human melanoma metastases. Oncoimmunology 3:e28963
Bartlett, Edmund K; Fetsch, Patricia A; Filie, Armando C et al. (2014) Human melanoma metastases demonstrate nonstochastic site-specific antigen heterogeneity that correlates with T-cell infiltration. Clin Cancer Res 20:2607-2616