Frontiers in Immunology (Nov 2024)
Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients
- Jonas S. Heitmann,
- Jonas S. Heitmann,
- Jonas S. Heitmann,
- Susanne Jung,
- Susanne Jung,
- Susanne Jung,
- Marcel Wacker,
- Marcel Wacker,
- Yacine Maringer,
- Yacine Maringer,
- Annika Nelde,
- Annika Nelde,
- Jens Bauer,
- Jens Bauer,
- Jens Bauer,
- Monika Denk,
- Monika Denk,
- Monika Denk,
- Naomi Hoenisch-Gravel,
- Naomi Hoenisch-Gravel,
- Marion Richter,
- Marion Richter,
- Marion Richter,
- Melek T. Oezbek,
- Melek T. Oezbek,
- Marissa L. Dubbelaar,
- Marissa L. Dubbelaar,
- Marissa L. Dubbelaar,
- Marissa L. Dubbelaar,
- Tatjana Bilich,
- Tatjana Bilich,
- Tatjana Bilich,
- Marina Pumptow,
- Peter Martus,
- Gerald Illerhaus,
- Claudio Denzlinger,
- Francesca Steinbach,
- Walter-Erich Aulitzky,
- Martin R. Müller,
- Daniela Dörfel,
- Hans–Georg Rammensee,
- Hans–Georg Rammensee,
- Hans–Georg Rammensee,
- Helmut R. Salih,
- Helmut R. Salih,
- Juliane S. Walz,
- Juliane S. Walz,
- Juliane S. Walz,
- Juliane S. Walz
Affiliations
- Jonas S. Heitmann
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
- Jonas S. Heitmann
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Jonas S. Heitmann
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Susanne Jung
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
- Susanne Jung
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Susanne Jung
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Marcel Wacker
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Marcel Wacker
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Yacine Maringer
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Yacine Maringer
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Annika Nelde
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Annika Nelde
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Jens Bauer
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Jens Bauer
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Jens Bauer
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany
- Monika Denk
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Monika Denk
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Monika Denk
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany
- Naomi Hoenisch-Gravel
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Naomi Hoenisch-Gravel
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Marion Richter
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Marion Richter
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Marion Richter
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany
- Melek T. Oezbek
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Melek T. Oezbek
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Marissa L. Dubbelaar
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Marissa L. Dubbelaar
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Marissa L. Dubbelaar
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany
- Marissa L. Dubbelaar
- Quantitative Biology Center (QBiC), University of Tübingen, Tübingen, Germany
- Tatjana Bilich
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Tatjana Bilich
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Tatjana Bilich
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany
- Marina Pumptow
- Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, Germany
- Peter Martus
- Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, Germany
- Gerald Illerhaus
- Department of Hematology, Oncology and Palliative Care, Katharinenhospital Stuttgart, Stuttgart, Germany
- Claudio Denzlinger
- Department of Oncology, Hematology and Palliative Care, Marienhospital Stuttgart, Stuttgart, Germany
- Francesca Steinbach
- Department of Hematology, Oncology and Palliative Care, Robert-Bosch-Krankenhaus, Stuttgart, Germany
- Walter-Erich Aulitzky
- Department of Hematology, Oncology and Palliative Care, Robert-Bosch-Krankenhaus, Stuttgart, Germany
- Martin R. Müller
- 0Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
- Daniela Dörfel
- 0Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
- Hans–Georg Rammensee
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Hans–Georg Rammensee
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany
- Hans–Georg Rammensee
- 1Institute of Immunology, University of Tübingen, Tübingen, Germany
- Helmut R. Salih
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
- Helmut R. Salih
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Juliane S. Walz
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany
- Juliane S. Walz
- Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany
- Juliane S. Walz
- Department of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, Germany
- Juliane S. Walz
- German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany
- DOI
- https://doi.org/10.3389/fimmu.2024.1482715
- Journal volume & issue
-
Vol. 15
Abstract
Cancer peptide vaccination represents a promising therapeutic approach, but has been hampered by lack of suitable antigens and restricted applicability due to different HLA backgrounds of individual patients. We here introduce a novel warehouse-based concept for composition of personalized peptide vaccines and report on its successful application in a Phase II clinical trial in patients with chronic lymphocytic leukemia (CLL) after first-line therapy. 26 CLL patients in at least partial remission (PR) after 6 months of immuno-chemotherapy were vaccinated with a personalized vaccine compiled from a premanufactured peptide warehouse comprising immunopeptidome-defined CLL-associated peptides. Primary objective was evaluation of immunogenicity, secondary objectives were safety and minimal residual disease (MRD) response. Immunopeptidome-guided vaccine composition was throughout successful, proving the feasibility of warehouse-based vaccine design. Vaccination was well tolerated, with local injection site reactions being the most common adverse event. Only few patients showed vaccine-induced T cell responses, attributable to their inability to mount strong immune responses due to immune-chemotherapy and lack of potent adjuvant formulations. Both issues are addressed within a follow-up trial (NCT04688385), combining the immunopeptidome-guided warehouse-based vaccine design reported here with a potent novel adjuvant evaluating personalized multi- peptide vaccination in CLL patients under T cell supportive BTK inhibitor therapies.Clinical trial registrationwww.clinicaltrialsregister.eu, identifier NCT02802943.
Keywords
