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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Veröffentlicht in:Frontiers in immunology 2024-11, Vol.15, p.1482715
Hauptverfasser: Heitmann, Jonas S, Jung, Susanne, Wacker, Marcel, Maringer, Yacine, Nelde, Annika, Bauer, Jens, Denk, Monika, Hoenisch-Gravel, Naomi, Richter, Marion, Oezbek, Melek T, Dubbelaar, Marissa L, Bilich, Tatjana, Pumptow, Marina, Martus, Peter, Illerhaus, Gerald, Denzlinger, Claudio, Steinbach, Francesca, Aulitzky, Walter-Erich, Müller, Martin R, Dörfel, Daniela, Rammensee, Hans-Georg, Salih, Helmut R, Walz, Juliane S
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Sprache:eng
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Zusammenfassung: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. www.clinicaltrialsregister.eu, identifier NCT02802943.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1482715