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

By B. Carreno, Vincent J. Magrini, M. Becker-Hapak, S. Kaabinejadian, Jasreet Hundal, Allegra Petti, Amy Ly, W. Lie, W. Hildebrand, Elaine R. Mardis and 1 more. Science, 2015

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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 Passenger mutations encode target melanoma antigens for human cancer immunotherapy. [Also see Perspective by Delamarre et al.] 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.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/d73aca5a4e3a9b3dcde7a21e995efc67a820cd30

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Citations in the corpus

Dendritic Cells and Cancer Immunity (2016, background): “The next generation use of vaccines containing patient-specific neoantigens will help to determine whether this has been a critical barrier to efficacy [79].”