报告题目：Neoantigen in Cancer Immunotherapy
Xiuli Zhang currently works as a Senior Scientist in the Department of Surgery, Washington University in Saint Louis. Her research focus on pre-clinical and clinical trial study of personalized cancer vaccine and immunotherapy. She has twenty years of research experiences in the area of vaccine development (cancer, virus, bacteria), mucosal immunology, cellular immunology and molecular microbiology, especially strong experience with T cell function in cancer immunotherapy with neoantigen and checkpoint blockade. Her work has extended to immunohistochemistry and confocal microscope areas with both section slide and whole tissue observation. She has authored more than 20 scienctific papers, which are published in the journals including nature, J Clin Invest, Cancer Immunology Research, PLoS Pathog, and J. Immunology.
Next-generation sequencing technologies have provided insights into the biology and mutational landscape of cancer. Here we evaluate the relevance of cancer neoantigens in murine cancer model (Sarcoma and breast cancer) and human cancers (breast cancer). we sequenced exomes of tumor and normal cells. We identified numerous nonsynonymous somatic mutations. A computational analysis identified and prioritized MHC class I–restricted candidate neoantigens expressed in the dominant tumor clone. Each candidate neoantigen was evaluated using peptide-binding assays, immunogenicity in vivo and in vitro, and preclinical models in which we measured antitumor immunity. Our results demonstrate that cancer neoantigens can be recognized by the immune system, and that CD8+ T cells enriched for prioritized cancer neoantigens were able to protect mice from tumor challenge. We conclude that next-generation sequencing and epitope-prediction strategies can identify and prioritize candidate neoantigens for immune targeting in breast cancer.