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

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

Research output: Contribution to journalArticlepeer-review

800 Scopus citations

Abstract

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-b 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.

Original languageEnglish
Pages (from-to)803-808
Number of pages6
JournalScience
Volume348
Issue number6236
DOIs
StatePublished - May 15 2015

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