Melanoma Neoantigen Discovery and Clinical Validation
Gerald P. Linette Center for Cellular Immunotherapies and Parker Institute for Cancer Immunotherapy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
T cell immunity directed against tumor encoded amino acid substitutions has been reported in humans with cancer, thus implicating missense mutations as a source of patient-specific neoantigens. We described a new strategy in 2015 to identify and validate human tumor neoantigens. Using next generation sequencing technologies with a novel bioinformatics pipeline, HLA class I restricted neoantigens were nominated among expressed melanoma missense mutations. Immunogenicity was evaluated using a novel personalized dendritic cell vaccine matured using 4 stimuli to promote IL-12p70 production. Our vaccination protocol increased the antigenic breadth and clonal diversity of neoantigen-specific CD8+ T cells in all patients treated. The neoantigen-specific CD8+ T cells are functional as examined using multiple in vitro assays. The mature DC vaccine is well tolerated without apparent side effect or autoimmune-related toxicities. Our findings together with recent reports from several other groups suggest that personalized cancer vaccines targeting private somatic tumor alterations may become feasible in the near future.
Credits: None available.
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