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

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.

• Authors: 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
• Journal: Science (New York, N.Y.) (Science) Vol. 348 Issue 6236 Pg. 803-8 (May 15 2015) ISSN: 1095-9203 [Electronic] United States
• PMID: 25837513 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Association for the Advancement of Science.

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Amino Acid Substitution (immunology)
• Antigen Presentation
• Antigens, Neoplasm (genetics, immunology)
• Cancer Vaccines (immunology, therapeutic use)
• Dendritic Cells (immunology, transplantation)
• HLA-A2 Antigen (genetics, immunology)
• Humans
• Immunotherapy, Active (methods)
• Melanoma (genetics, immunology, therapy)
• Monitoring, Immunologic
• Mutation
• Receptors, Antigen, T-Cell, alpha-beta (immunology)
• Skin Neoplasms (genetics, immunology, therapy)
• T-Lymphocytes (immunology)