Melanoma Neoantigen Discovery and Clinical Validation

Identification: Linette, Gerald
Publication Date: March 30, 2018
Expiration Date: April 23, 2019


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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