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

Science  15 May 2015:
Vol. 348, Issue 6236, pp. 803-808
DOI: 10.1126/science.aaa3828

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Giving antitumor T cells a boost

Mutations allow tumors to divide, escape death, and resist treatment. But mutations can also cause tumors to express mutant proteins, which could potentially be exploited to drive antitumor T cell responses. Carreno et al. report the results of a small phase I trial seeking to do just this (see the Perspective by Delamarre et al.). They vaccinated three patients with advanced melanoma with personalized dendritic cell–based vaccines designed to activate T cells specific for mutations in the patients' cancer. T cells specific for mutant peptides did indeed expand. A next step will be to determine whether this promising strategy improves patient outcomes.

Science, this issue p. 803; see also p. 760

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-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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