Publikation
Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia
Wissenschaftlicher Artikel/Review - 08.07.2021
Nelde Annika, Rammensee Hans-Georg, Aulitzky Walter Erich, Illerhaus Gerald, Denzlinger Claudio, Neidert Marian Christoph, Bauer Jens, Marcu Ana, Heitmann Jonas S, Roerden Malte, Salih Helmut R, Bilich Tatjana, Maringer Yacine, Walz Juliane S
Bereiche
PubMed
DOI
Zitation
Art
Zeitschrift
Veröffentlichungsdatum
eISSN (Online)
Seiten
Kurzbeschreibung/Zielsetzung
Antigen-specific immunotherapies, in particular peptide vaccines, depend on the recognition of naturally presented antigens derived from mutated and unmutated gene products on human leukocyte antigens, and represent a promising low-side-effect concept for cancer treatment. So far, the broad application of peptide vaccines in cancer patients is hampered by challenges of time- and cost-intensive personalized vaccine design, and the lack of neoepitopes from tumor-specific mutations, especially in low-mutational burden malignancies. In this study, we developed an immunopeptidome-guided workflow for the design of tumor-associated off-the-shelf peptide warehouses for broadly applicable personalized therapeutics. Comparative mass spectrometry-based immunopeptidome analyses of primary chronic lymphocytic leukemia (CLL) samples, as representative example of low-mutational burden tumor entities, and a dataset of benign tissue samples enabled the identification of high-frequent non-mutated CLL-associated antigens. These antigens were further shown to be recognized by pre-existing and induced T cells in CLL patients and healthy volunteers, and were evaluated as pre-manufactured warehouse for the construction of personalized multi-peptide vaccines in a first clinical trial for CLL (NCT04688385). This workflow for the design of peptide warehouses is easily transferable to other tumor entities and can provide the foundation for the development of broad personalized T cell-based immunotherapy approaches.