Dataset Information

Immunopeptidomics-guided warehouse design for peptide-based immunotherapy in chronic lymphocytic leukemia

ABSTRACT: In recent years the clinical success of T cell-based immunotherapy approaches has revolutionized treatment of solid tumors and hematological malignancies. However, still some patients do not respond to available therapies at all, others for limited time only. A promising low side-effect approach is peptide-based immunotherapy, which relies on specific immune recognition of tumor-associated human leucocyte antigen (HLA)-presented peptides. In this study, we developed a workflow for the immunopeptidome-guided design of off-the shelf warehouses for personalized peptide vaccines using the example of chronic lymphocyte leukemia (CLL). The so defined warehouses could provide the basis for different T cell-based immunotherapy approaches such as TCR-engineered T cell transfer or multi-peptide vaccinations. The warehouse approach enables a fast and cost-effective way to provide a personalized T cell-based immunotherapeutic approach. The here defined peptide warehouse is already utilized for a personalized multi-peptide vaccine trial (iVAC-XS15-CLL01, NCT04688385).

INSTRUMENT(S): Orbitrap Fusion Lumos, LTQ Orbitrap XL

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Peripheral Blood Mononuclear Cell

DISEASE(S): Chronic Lymphocytic Leukemia

SUBMITTER: Annika Nelde

LAB HEAD: Juliane S. Walz

PROVIDER: PXD024871 | Pride | 2021-09-10

REPOSITORIES: Pride

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Publications

Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia.

Nelde Annika A Maringer Yacine Y Bilich Tatjana T Salih Helmut R HR Roerden Malte M Heitmann Jonas S JS Marcu Ana A Bauer Jens J Neidert Marian C MC Denzlinger Claudio C Illerhaus Gerald G Aulitzky Walter Erich WE Rammensee Hans-Georg HG Walz Juliane S JS

Frontiers in immunology 20210708

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 l ...[more]

PMID: 34305947

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Project description:Biomaterials play an increasing role in clinical applications and regenerative medicine. Modern biomaterials should imitate the function of damaged tissue without triggering an immune response, initiate self-regeneration of the body and gradually degrade after implantation. The immune system is now well recognized to play a major role in influencing the biocompatibility of implanted medical devices. To develop a better understanding of the effects of biomaterials on the immune response, we have developed a highly sensitive novel test system capable of examining changes in the immune system by biomaterial. Here, we evaluate for the first time the immunopeptidome, a highly sensitive system that reflects cancer transformation, virus or drug influences and passes these changes directly to T cells, as a test system to examine the effects of contact with materials. Since monocytes are one of the first immune cells reacting to biomaterials, we have tested the influence of different materials - stainless steel, aluminum, zinc, high-density polyethylene, polyurethane films containing zinc diethyldithiocarbamate, copper, and zinc sulphate - on the monocytic THP-1 cell line. Material-associated peptides were identified after stimulation with all material types examined. The magnitude of induced changes in the immunopeptidome after the stimulation appears comparable to that of bacterial lipopolysaccharides (LPS). The source proteins of many detected peptides are associated with cytotoxicity, fibrosis, autoimmunity, inflammation and cellular stress. Considering all tested materials, it was found that the LPS-induced cytotoxicity-, inflammation- and cellular stress-associated HLA class I peptides were mainly induced by aluminum and HLA class II peptides mainly by stainless steel. These findings provide some of the first insights into the effects on the immunopeptidome by biomaterials. A more thorough understanding of these effects may enable the design of more biocompatible implant materials using in vitro models in future. This may be achieved through developing a deeper understanding of possible immune responses induced by biomaterials such as fibrosis, inflammation, cytotoxicity, and autoimmune reactions.

Dataset Information

Immunopeptidomics-guided warehouse design for peptide-based immunotherapy in chronic lymphocytic leukemia

Publications

Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia.

Similar Datasets

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