A phase 1 study of VAC85135, a neoantigen vaccine regimen targeting calreticulin and JAK2 mutations, in combination with ipilimumab in patients with myeloproliferative neoplasms
Rattachement africain : us, gb. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Disease-specific somatic mutations (mut) in calreticulin ( CALR ) and JAK2 ( JAK2V617F ) are drivers of myeloproliferative neoplasms (MPNs), causing generation of immunogenic peptide epitopes hypothesized to be vaccine-targetable neoantigens. VAC85135, a heterologous prime-boost vaccine regimen comprising adenoviral and vaccinia vectors encoding polypeptides specific to mutCALR and JAK2V617F , concurrent with anti-CTLA-4, ipilimumab, was investigated in a phase 1 study. Fourteen (myelofibrosis [MF], n = 10, essential thrombocythemia [ET], n = 4; mutCALR , n = 12, JAK2V617F , n = 2) patients were enrolled across three cohorts. A safety lead-in cohort (C0) received VAC85135 alone by intramuscular injection. Following acceptable tolerability, intramuscular VAC85135 was co-administered with intravenous ipilimumab: 1 mg/kg (C1) or 3 mg/kg (C2). Antigen-specific T-cell immune responses were analyzed by IFN-γ ELISpot. Clinical responses were evaluated per IWG-MRT-ELN criteria. Treatment-related adverse events were reported in 64.3% of patients; mostly Grade 1/2. Positive immune responses to mutCALR were observed post-vaccination in 5/14 (35.7%) patients. Immune response was maintained in one C0 patient over the treatment duration starting after dose 3; responses in four C1 patients were transient and observed after dose 7 in 2/4 patients. No patients had reduced mutCALR or JAK2V617F mutant allele burden at any post-vaccination timepoint. Consistent reductions in reticulin fibrosis were not observed in post-vaccination bone marrow biopsies. Best overall response was stable disease in nine patients with MF and no response in four patients with ET. The absence or delayed onset of immune response in most patients suggest VAC85135 was poorly immunogenic and unable to generate productive CALR or JAK2 neoantigen antitumor immunity. ClinicalTrials.gov identifier: NCT05444530.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A phase 1 study of VAC85135, a neoantigen vaccine regimen targeting calreticulin and JAK2 mutations, in combination with ipilimumab in patients with myeloproliferative neoplasms
- Date Crossref
- 24/08/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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City Of Hope National Medical Center Department of Hematology and Hematopoietic Cell Transplantation pays non établi dans la noticeÉtablissement de santé
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Churchill Hospital pays non établi dans la noticeÉtablissement de santé
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Moffitt Cancer Center pays non établi dans la noticeÉtablissement de santé
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Cleveland Clinic Department of Hematology and Medical Oncology pays non établi dans la noticeÉtablissement de santé
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The Christie Hospital Department of Haematology pays non établi dans la noticeÉtablissement de santé
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The University of Texas MD Anderson Cancer Center Department of Leukemia pays non établi dans la noticeÉtablissement de santé
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Johnson & Johnson (United States) pays non établi dans la noticeEntreprise
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Guy's and St Thomas' NHS Foundation Trust Department of Haematology pays non établi dans la noticeÉtablissement de santé
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Oxford University NHS Trust and University of Oxford Department of Haematology pays non établi dans la noticeUniversité ou école supérieure
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Department of Malignant Hematology pays non établi dans la noticeInstitution
Department of Hematology and Hematopoietic Cell Transplantation — City Of Hope National Medical Center, Churchill Hospital et Moffitt Cancer Center, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.