Chasing neoantigens; invite naïve T cells to the party. (April 2022)

• Record Type: Journal Article
• Authors: Bollineni, Ravi Chand; Tran, Trung T; Lund-Johansen, Fridtjof; Olweus, Johanna
• Is Part Of: Current opinion in immunology. Volume 75(2022)
• Publication Date: 2022-04
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2022.102172
• Languages: English
• ISSNs: 0952-7915

Abstract

Abstract : Neoantigens are commonly defined as HLA-bound peptides that are altered as a consequence of DNA damage and recognized by T cells. Current efforts to target neoantigens in therapy rely on algorithms that predict HLA-binding and immunogenicity from DNA sequence data. Datasets obtained by mass spectrometry of peptides eluted from mono-allelic cell lines have greatly improved our ability to predict HLA-binding. The main challenge lies in selecting those that are likely to be immunogenic. Here we argue that the current approach of searching for antigens that have evoked T-cell responses in untreated patients may underestimate immunogenicity. Results from clinical trials show that cancer vaccines often primarily engage the naïve T-cell repertoire. We therefore propose a new pipeline where HLA-binding is detected directly by mass spectrometry and immunogenicity is determined as the ability to prime naïve T cells from healthy donors.