Cancer immunotherapy. 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, 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
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.
Trial registration: ClinicalTrials.gov NCT00683670.
Copyright © 2015, American Association for the Advancement of Science.
Figures
![Fig. 1. Vaccine candidate identification and immune…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4549796/bin/nihms-713231-f0001.jpg)
![Fig. 2. Antigenic determinants recognized by vaccine-induced…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4549796/bin/nihms-713231-f0002.jpg)
![Fig. 3. Processing and presentation of tumor…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4549796/bin/nihms-713231-f0003.jpg)
![Fig. 4. Vaccination promotes a diverse neoantigen-specific…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4549796/bin/nihms-713231-f0004.jpg)
Source: PubMed