In recent years, immunotherapy, i.e. the specific induction of anti-tumor immune responses, has revolutionized the treatment of cancer. However, such immunotherapeutic approaches are not yet available for all cancer entities and many patients often do not respond or only respond for a limited time to currently available therapeutic options. Here, peptide-based immunotherapy represents a comparatively low side-effect option for inducing specific immune responses against tumor cells in patients.
Research
Peptide-based immunotherapy offers a comparatively low side-effect option for inducing specific immune responses against tumor cells in patients. Peptides are short protein fragments that each body cell presents on its surface to the T cells of the immune system on so-called human leukocyte antigens (HLA).
Tumor cells and also virus-infected cells differ from healthy cells and thus enable the immune system to recognize them as foreign. These so-called tumor-associated peptides are the key to a targeted immune response against the tumor cells, which can be activated by peptide-based immunotherapies and thus used to fight the tumor.
However, peptide-based immunotherapy need not be limited to tumor diseases. This technique can also be used for immunization or targeted boosting of T cells in viral infections.
Research focus
Research focus
The research area of our department has three main focuses:
Mass spectrometry
For the identification of HLA-presented peptides, we employ tissue or cell samples from patients or healthy donors as well as cell lines cultivated in the laboratory. In the lab, we can isolate the peptides from the surface of the cells and then utilize mass spectrometry, which allows us to identify these HLA-presented peptides. By comparing healthy tissue with tumor tissue, we can then identify those peptides that are highly abundant and exclusively presented on tumor cells but never on healthy tissue. In addition, we use label-free quantification to investigate the dynamic changes of the immunopeptidome under specific tumor therapies and cell stress mechanisms with the aim to develop new combinatorial therapeutic strategies.
For mass spectrometric immunopeptidome analysis, two state-of-the-art mass spectrometers are currently available (Orbitrap Fusion Lumos and Q-Exactive HF) as well as a new timsTOF Pro instrument, which allows high-throughput measurements of large numbers of samples and a sensitive analysis of the immunopeptidome. |
T cells
For the further development of peptide-based immunotherapies, it is important to characterize the previously identified tumor-associated peptides, i.e. to determine whether they are recognized by and can activate peptide-specific T cells. This includes the investigation of the general functionality of the T cell compartment in tumor patients and its modulation by other therapies as well as the detailed characterization of antigen-specific T cell responses down to the single cell level.
For this purpose, we use various state-of-the-art methods and procedures of T cell analysis such as ELISpot assays and flow cytometry. |
Bioinformatics
The bioinformatic team has an important role in our department as it processes our highly complex data generated by mass spectrometry and other omics technologies (genomics, transcriptomics, metabolomics, etc). Using existing and novel approaches, it assists us in identifying potential new immunotherapy targets. In addition, members of the team work closely with the Center for Quantitative Biology. This collaboration allows us to use and further co-develop validated bioinformatics workflows, which are then freely available to other researchers.
Current research projects
Current research projects
COVID-19
T-cell-based immunity not only plays an important role in tumor diseases, but is also crucial for the defense against viral infections.
Learn moreTumor diseases
The main focus of the Peptide-based Immunotherapy Department is the development of clinically effective peptide-based vaccination approaches for tumor patients.
Learn morePublications and prices
Publications and awards
Selected publications
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2024
Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade.
Wyss N, Berner F, Walter V, Jochum AK, Purde MT, Abdou MT, Sinnberg T, Hofmeister K, Pop OT, Hasan Ali O, Bauer J, Cheng HW, Lütge M, Klümper N, Diem S, Kosaloglu-Yalcin Z, Zhang Y, Sellmer L, Macek B, Karbach J, König D, Läubli H, Zender L, Meyer BS, Driessen C, Schürch CM, Jochum W, Amaral T, Heinzerling L, Cozzio A, Hegazy AN, Schneider T, Brutsche MH, Sette A, Lenz TL, Walz J, Rammensee HG, Früh M, Jäger E, Becher B, Tufman A, Nuñez N, Joerger M, Flatz L.
Am J Respir Crit Care Med. 2024 Apr 16
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2024
FusionVAC22_01: a phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion.
Hackenbruch C, Bauer J, Heitmann JS, Maringer Y, Nelde A, Denk M, Zieschang L, Kammer C, Federmann B, Jung S, Martus P, Malek NP, Nikolaou K, Salih HR, Bitzer M, Walz JS.
Front Oncol. 2024 Mar 28
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2024
Protocol of a first in human clinical trial to evaluate the safety, tolerability and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3).
Jung S, Schlenk RF, Hackenbruch C, Pinzon SSL, Bitzer M, Pflügler M, Walz JS, Jung G, Heitmann JS, Salih HR.
Front Oncol. 2024 Feb
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2023
Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults.
Tandler C, Heitmann JS, Michel TM, Marconato M, Jaeger SU, Tegeler CM, Denk M, Richter M, Oezbek MT, Maringer Y, Schroeder SM, Schneiderhan-Marra N, Wiesmüller KH, Bitzer M, Ruetalo N, Schindler M, Meisner C, Fischer I, Rammensee HG, Salih HR, Walz JS.
Int J Infect Dis. 2023 Nov 26
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2023
TOFIMS mass spectrometry-based immunopeptidomics refines tumor antigen identification.
Hoenisch Gravel N, Nelde A, Bauer J, Mühlenbruch L, Schroeder SM, Neidert MC, Scheid J, Lemke S, Dubbelaar ML, Wacker M, Dengler A, Klein R, Mauz PS, Löwenheim H, Hauri-Hohl M, Martin R, Hennenlotter J, Stenzl A, Heitmann JS, Salih HR, Rammensee HG, Walz JS.
Nat Commun. 2023 Nov 17
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2023
DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts.
Goyal A, Bauer J, Hey J, Papageorgiou DN, Stepanova E, Daskalakis M, Scheid J, Dubbelaar M, Klimovich B, Schwarz D, Märklin M, Roerden M, Lin YY, Ma T, Mücke O, Rammensee HG, Lübbert M, Loayza-Puch F, Krijgsveld J, Walz JS, Plass C.
Nat Commun. 2023 Oct 23
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2023
Immune surveillance of acute myeloid leukemia is mediated by HLA-presented antigens on leukemia progenitor cells.
Nelde A, Schuster H, Heitmann JS, Bauer J, Maringer Y, Zwick M, Volkmer JP, Chen JY, Paczulla Stanger AM, Lehmann A, Appiah B, Märklin M, Rücker-Braun E, Salih HR, Roerden M, Schroeder SM, Häring MF, Schlosser A, Schetelig J, Schmitz M, Boerries M, Köhler N, Lengerke C, Majeti R, Weissman IL, Rammensee HG, Walz JS.
Blood Cancer Dis. 2023 Nov
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2023
Long-Term Follow-Up of COVID-19 Convalescents—Immune Response Associated with Reinfection Rate and Symptoms.
Seller A, Hackenbruch C, Walz JS, Nelde A, Heitmann JS.
Viruses 2023, 15(10)
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2023
Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency.
Heitmann JS, Tandler C, Marconato M, Nelde A, Habibzada T, Rittig SM, Tegeler CM, Maringer Y, Jaeger SU, Denk M, Richter M, Oezbek MT, Wiesmüller KH, Bauer J, Rieth J, Wacker M, Schroeder SM, Hoenisch Gravel N, Scheid J, Märklin M, Henrich A, Klimovich B, Clar KL, Lutz M, Holzmayer S, Hörber S, Peter A, Meisner C, Fischer I, Löffler MW, Peuker CA, Habringer S, Goetze TO, Jäger E, Rammensee HG, Salih HR, Walz JS.
Nat Commun. 2023 Aug 18
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2023
Phase I study evaluating the Fc-optimized FLT3 antibody FLYSYN in AML patients with measurable residual disease.
Heitmann JS, Schlenk RF, Dörfel D, Kayser S, Döhner K, Heuser M, Thol F, Kapp-Schwoerer S, Labrenz J, Edelmann D, Märklin M, Vogel W, Bethge W, Walz JS, Große-Hovest L, Steiner M, Jung G, Salih HR.
J Hematol Oncol. 2023 Aug 17
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2023
Immunoprecipitation methods impact the peptide repertoire in immunopeptidomics.
Wacker M, Bauer J, Wessling L, Dubbelaar M, Nelde A, Rammensee HG, Walz JS.
Front Immunol. 2023 Jul 21
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2023
A T-cell antigen atlas for meningioma: novel options for immunotherapy.
Medici G, Freudenmann LK, Velz J, Wang SS, Kapolou K, Paramasivam N, Mühlenbruch L, Kowalewski DJ, Vasella F, Bilich T, Frey BM, Dubbelaar ML, Patterson AB, Zeitlberger AM, Silginer M, Roth P, Weiss T, Wirsching HG, Krayenbühl N, Bozinov O, Regli L, Rammensee HG, Rushing EJ, Sahm F, Walz JS, Weller M, Neidert MC.
Acta Neuropathol. 2023 Jun 27
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2023
Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma.
Naghavian R, Faigle W, Oldrati P, Wang J, Toussaint NC, Qiu Y, Medici G, Wacker M, Freudenmann LK, Bonté PE, Weller M, Regli L, Amigorena S, Rammensee HG, Walz JS, Brugger SD, Mohme M, Zhao Y, Sospedra M, Neidert MC, Martin R.
Nature. 2023 May 17
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2023
Elevated SARS-CoV-2-Specific Antibody Levels in Patients with Post-COVID Syndrome.
Hackenbruch C, Maringer Y, Tegeler CM, Walz JS, Nelde A, Heitmann JS.
Viruses 2023, 15(3), 701
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2023
Antibody Binding and Angiotensin-Converting Enzyme 2 Binding Inhibition Is Significantly Reduced for Both the BA.1 and BA.2 Omicron Variants.
Junker D, Becker M, Wagner TR, Kaiser PD, Maier S, Grimm TM, Griesbaum J, Marsall P, Gruber J, Traenkle B, Heinzel C, Pinilla YT, Held J, Fendel R, Kreidenweiss A, Nelde A, Maringer Y, Schroeder S, Walz JS, Althaus K, Uzun G, Mikus M, Bakchoul T, Schenke-Layland K, Bunk S, Haeberle H, Göpel S, Bitzer M, Renk H, Remppis J, Engel C, Franz AR, Harries M, Kessel B, Lange B, Strengert M, Krause G, Zeck A, Rothbauer U, Dulovic A, Schneiderhan-Marra N.
Clin Infect Dis. 2023 Feb 8;76(3):e240-e249
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2023
The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination.
Mühlenbruch L, Abou-Kors T, Dubbelaar ML, Bichmann L, Kohlbacher O, Bens M, Thomas J, Ezić J, Kraus JM, Kestler HA, von Witzleben A, Mytilineos J, Fürst D, Engelhardt D, Doescher J, Greve J, Schuler PJ, Theodoraki MN, Brunner C, Hoffmann TK, Rammensee HG, Walz JS, Laban S.
Br J Cancer. 2023 Feb 23:1-11
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2023
Viral T-cell epitopes - Identification, characterization and clinical application
Schroeder S.M, Nelde A, Walz JS.
Elsevier, 2023 Jan 25;66:101725
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2022
Prevalence of COVID-19-associated symptoms during acute infection in relation to SARS-CoV-2-directed humoral and cellular immune responses in a mild-diseased convalescent cohort.
Tegeler CM, Bilich T, Maringer Y, Salih HR, Walz JS, Nelde A, Heitmann JS.
Int J Infect Dis. 2022 Jul;120:187-195
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2022
Durable spike-specific T cell responses after different COVID-19 vaccination regimens are not further enhanced by booster vaccination.
Maringer Y, Nelde A, Schroeder SM, Schuhmacher J, Hörber S, Peter A, Karbach J, Jäger E, Walz JS.
Sci Immunol. 2022 Dec 23;7(78):eadd3899
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2022
Increased soluble HLA in COVID-19 present a disease-related, diverse immunopeptidome associated with T cell immunity.
Nelde A, Rieth J, Roerden M, Dubbelaar ML, Hoenisch Gravel N, Bauer J, Klein R, Hoheisel T, Mahrhofer H, Göpel S, Bitzer M, Hörber S, Peter A, Heitmann JS, Walz JS.
iScience. 2022 Dec 22;25(12):105643
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2022
The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma.
Bauer J, Köhler N, Maringer Y, Bucher P, Bilich T, Zwick M, Dicks S, Nelde A, Dubbelaar M, Scheid J, Wacker M, Heitmann JS, Schroeder S, Rieth J, Denk M, Richter M, Klein R, Bonzheim I, Luibrand J, Holzer U, Ebinger M, Brecht IB, Bitzer M, Boerries M, Feucht J, Salih HR, Rammensee HG, Hailfinger S, Walz JS.
Nat Commun. 2022 Oct 27;13(1):6401
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2022
Immunopeptidome Diversity in Chronic Lymphocytic Leukemia Identifies Patients with Favorable Disease Outcome.
Marconato M, Maringer Y, Walz JS, Nelde A, Heitmann JS.
Cancers (Basel). 2022 Sep 25;14(19):4659
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2022
HLA-DR Presentation of the Tumor Antigen MSLN Associates with Clinical Outcome of Ovarian Cancer Patients.
Tegeler CM, Scheid J, Rammensee HG, Salih HR, Walz JS, Heitmann JS, Nelde A.
Cancers (Basel). 2022. Apr 30;14(9):2260.
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2022
Upstream open reading frames regulate translation of cancer-associated transcripts and encode HLA-presented immunogenic tumor antigens.
Nelde A*, Flötotto L*, Jürgens L, Szymik L, Hubert E, Bauer J, Schliemann C, Kessler T, Lenz G, Rammensee HG, Walz JS*, Wethmar K*.
Cellular and Molecular Life Science. 2022. Mar;79(3):171.
*Authors contributed equally to this work.
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2021
A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity.
Heitmann JS*, Bilich T*, Tandler C*, Nelde A, Maringer Y, Marconato M, Reusch J, Jäger S, Denk M, Richter M, Anton L, Weber LM, Roerden M, Bauer J, Rieth J, Wacker M, Hörber S, Peter A, Meisner C, Fischer I, Löffler MW, Karbach J, Jäger E, Klein R, Rammensee HG, Salih HR, Walz JS.
Nature. 2021: 1-9.
*Authors contributed equally to this work.
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2021
Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia.
Nelde A*, Maringer Y*, Bilich T, Salih HR, Roerden M, Heitmann JS, Marcu A, Bauer J, Neidert MC, Denzlinger C, Illerhaus G, Aulitzky WE, Rammensee HG, Walz JS.
Front Immunol 2021; 12:2731
*Authors contributed equally to this work.
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2021
Preexisting and Post-COVID-19 Immune Responses to SARS-CoV-2 in Patients with Cancer.
Bilich T*, Roerden M*, Maringer Y, Nelde A, Heitmann JS, Dubbelaar ML, Peter A, Horber S, Bauer J, Rieth J, Wacker M, Berner F, Flatz L, Held S, Brossart P, Märklin M, Wagner P, Erne E, Klein R, Rammensee H-G, Salih HR, Walz JS.
Cancer Discovery. 2021 Aug 1; (11) (8) 1982-1995.
*Authors contributed equally to this work.
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2021
T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune responses in COVID-19 convalescent individuals.
Bilich T*, Nelde A*, Heitmann JS*, Maringer Y, Roerden M, Bauer J, Rieth J, Wacker M, Peter A, Hörber S, Rachfalski D, Märklin M, Stevanović S, Rammensee HG, Salih HR, Walz JS.
Sci Transl Med 2021; Apr 21;13(590):eabf7517
*Authors contributed equally to this work.
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2021
SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T-cell recognition.
Nelde A*, Bilich T*, Heitmann JS*, Maringer Y, Salih HR, Roerden M, Lübke M, Bauer J, Rieth J, Wacker M, Peter A, Hörber S, Traenkle B, Kaiser PD, Rothbauer U, Becker M, Junker D, Krause G, Strengert M, Schneiderhan-Marra N, Templin MF, Joos TO, Kowalewski DJ, Stos-Zweifel V, Fehr M, Rabsteyn A, Mirakaj V, Karbach J, Jäger E, Graf M, Gruber LC, Rachfalski D, Preuß B, Hagelstein I, Märklin M, Bakchoul T, Gouttefangeas C, Kohlbacher O, Klein R, Stevanović S, Rammensee HG, Walz JS.
Nature Immunology 2021; 22(1):74-85.
*Authors contributed equally to this work.
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2020
Mass spectrometry-based identification of a BCMA-derived T-cell epitope for antigen-specific immunotherapy in multiple myeloma.
Bilich T, Nelde A, Bauer J, Walz S, Roerden M, Salih HR, Weisel K, Besemer B, Marcu A, Lübke M, Schuhmacher J, Neidert MC, Rammensee H-G, Stevanović S, and Walz JS.
Blood Cancer J 2020; 10(2):24.
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2019
The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy.
Bilich T*, Nelde A*, Bichmann L, Roerden M, Salih HR, Kowalewski DJ, Schuster H, Tsou CC, Marcu A, Neidert MC, Lübke M, Rieth J, Schemionek M, Brümmendorf TH, Vucinic V, Niederwieser D, Bauer J, Märklin M, Peper JK, Klein R, Kohlbacher O, Kanz L, Rammensee HG, Stevanović S, and Walz JS.
Blood 2019; 133 (6): 550-565.
*Authors contributed equally to this work.
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2016
Carfilzomib alters the HLA-presented peptidome of myeloma cells and impairs presentation of peptides with aromatic C-termini.
Kowalewski DJ, Walz S, Backert L, Schuster H, Kohlbacher O, Weisel K, Rittig SM, Kanz L, Salih HR, Rammensee HG, Stevanović S, Stickel JS.
Blood Cancer J. 2016 Apr 8;6(4):e411.
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2015
The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy.
Walz S, Stickel JS, Kowalewski DJ, Schuster H, Weisel K, Backert L, Kahn S, Nelde A, Stroh T, Kohlbacher O, Kanz L, Salih HR, Rammensee HG, Stevanovic S.
Blood 2015; 126:1203-13.
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2015
HLA ligandome analysis identifies the underlying specificities of spontaneous antileukemia immune responses in chronic lymphocytic leukemia (CLL).
Kowalewski DJ, Schuster H, Backert L, Berlin C, Kahn S, Kanz L, Salih HR, Rammensee HG, Stevanovic S, Stickel JS.
Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):E166-75.
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2015
Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted approach toward peptide-based immunotherapy.
Berlin C, Kowalewski DJ, Schuster H, Mirza N, Walz S, Handel M, Schmid-Horch B, Salih HR, Kanz L, Rammensee HG, Stevanović S, Stickel JS.
Leukemia. 2015 Mar;29(3):647-59.
Awards
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2023
Waltraud-Lewenz-Preis, Heidelberg an Jens Bauer
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2022
International Immunocompromised Host Society (ICHS) Takeda Virology Award an Juliane Walz
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2022
Best Abstract Award, DGHO, Wien an Juliane Walz
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2021
Best Abstract Award DGHO Jahrestagung Berlin an Juliane Walz
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2020
Promotionspreis der Reinhold-und-Maria-Teufel-Stiftung an Annika Nelde
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2020
„Poster Award“ of the University Tübingen, research colloquium an Juliane Walz
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2018
„Posterpreis“ DGHO Wien an Juliane Walz
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2018
Young Investigator Preis der DGHO an Annika Nelde
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2017
“Posterpreis“ of the University Tübingen, research colloquium an Juliane Walz
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2016
Young Investigator Award DGHO Leipzig an Juliane Walz
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2015
"Posterpreis“ DGHO Basel an Juliane Walz
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2015
Württembergischer Krebspreis an Juliane Walz
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2014
Abstract Achievement Award American Society of Hematology an Juliane Walz
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2013
Abstract Achievement Award American Society of Hematology an Juliane Walz
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2012
Abstract Achievement Award American Society of Hematology an Juliane Walz
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2011
Promotionspreis der Universität Tübingen an Juliane Walz
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2011
Ludolf Krehl Promotionspreis der Süddeutschen Gesellschaft für Innere Medizin an Juliane Walz
