A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells

作者：Beatriz M. Carreno, Vincent Magrini, Michelle Becker‐Hapak, Saghar Kaabinejadian, Jasreet Hundal, Allegra A. Petti, Amy Ly, Wen‐Rong Lie, William H. Hildebrand, Elaine R. Mardis, Gerald P. Linette · 发表于：Science · 年份：2015 · DOI：10.1126/science.aaa3828 · 被引用次数：1306 · 研究领域：Immunotherapy and Immune Responses、vaccines and immunoinformatics approaches、Cancer Immunotherapy and Biomarkers

T cell immunity directed against tumor-encoded amino acid substitutions occurs in some melanoma patients. This implicates missense mutations as a source of patient-specific neoantigens. However, a systematic evaluation of these putative neoantigens as targets of antitumor immunity is lacking. Moreover, it remains unknown whether vaccination can augment such responses. We found that a dendritic cell vaccine led to an increase in naturally occurring neoantigen-specific immunity and revealed previously undetected human leukocyte antigen (HLA) class I-restricted neoantigens in patients with advanced melanoma. The presentation of neoantigens by HLA-A*02:01 in human melanoma was confirmed by mass spectrometry. Vaccination promoted a diverse neoantigen-specific T cell receptor (TCR) repertoire in terms of both TCR-β usage and clonal composition. Our results demonstrate that vaccination directed at tumor-encoded amino acid substitutions broadens the antigenic breadth and clonal diversity of antitumor immunity.