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

BM Carreno, V Magrini, M Becker-Hapak… - Science, 2015 - science.org
BM Carreno, V Magrini, M Becker-Hapak, S Kaabinejadian, J Hundal, AA Petti, A Ly, WR Lie
Science, 2015science.org
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 …
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.
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