Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients
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 v...
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Frontiers Media S.A.
2024-11-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Jonas S. Heitmann |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4e1b48fe04f94a3ea04c70520a8bf38c |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-4e1b48fe04f94a3ea04c70520a8bf38c2024-11-26T05:10:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14827151482715Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patientsJonas S. Heitmann0Jonas S. Heitmann1Jonas S. Heitmann2Susanne Jung3Susanne Jung4Susanne Jung5Marcel Wacker6Marcel Wacker7Yacine Maringer8Yacine Maringer9Annika Nelde10Annika Nelde11Jens Bauer12Jens Bauer13Jens Bauer14Monika Denk15Monika Denk16Monika Denk17Naomi Hoenisch-Gravel18Naomi Hoenisch-Gravel19Marion Richter20Marion Richter21Marion Richter22Melek T. Oezbek23Melek T. Oezbek24Marissa L. Dubbelaar25Marissa L. Dubbelaar26Marissa L. Dubbelaar27Marissa L. Dubbelaar28Tatjana Bilich29Tatjana Bilich30Tatjana Bilich31Marina Pumptow32Peter Martus33Gerald Illerhaus34Claudio Denzlinger35Francesca Steinbach36Walter-Erich Aulitzky37Martin R. Müller38Daniela Dörfel39Hans–Georg Rammensee40Hans–Georg Rammensee41Hans–Georg Rammensee42Helmut R. Salih43Helmut R. Salih44Juliane S. Walz45Juliane S. Walz46Juliane S. Walz47Juliane S. Walz48Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, GermanyQuantitative Biology Center (QBiC), University of Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, GermanyInstitute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, GermanyInstitute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, GermanyDepartment of Hematology, Oncology and Palliative Care, Katharinenhospital Stuttgart, Stuttgart, GermanyDepartment of Oncology, Hematology and Palliative Care, Marienhospital Stuttgart, Stuttgart, GermanyDepartment of Hematology, Oncology and Palliative Care, Robert-Bosch-Krankenhaus, Stuttgart, GermanyDepartment of Hematology, Oncology and Palliative Care, Robert-Bosch-Krankenhaus, Stuttgart, Germany0Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany0Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany1Institute of Immunology, University of Tübingen, Tübingen, GermanyClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, GermanyCluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, GermanyDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital Tübingen, Tübingen, GermanyGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, GermanyCancer 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1482715/fullCLLvaccinepeptidewarehouseimmunopeptidometrial |
| spellingShingle | 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 Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients Frontiers in Immunology CLL vaccine peptide warehouse immunopeptidome trial |
| title | Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients |
| title_full | Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients |
| title_fullStr | Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients |
| title_full_unstemmed | Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients |
| title_short | Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients |
| title_sort | warehouse based immunopeptidome guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in cll patients |
| topic | CLL vaccine peptide warehouse immunopeptidome trial |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1482715/full |
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