P06.05.A INTRACEREBROVENTRICULAR TCR-TRANSGENIC T CELL THERAPY TO TREAT GLIOBLASTOMA (INVENT4GB)
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Le résumé fourni par la source
Abstract BACKGROUND Novel concepts in immunotherapy have evolved with the identification of potential (neo)epitopes and/or combinations with immune checkpoint inhibitors (ICI). In contrast to many other solid tumors, ICI have not improved outcome for patients with glioblastoma (GB) in phase 3 studies. However, antigen-specific T cells induced by vaccines or adoptively transferred as chimeric antigen receptor (CAR) T cells produced encouraging responses in early clinical trials and case series. From one of these trials, the Actively Personalized Vaccine Consortium (GAPVAC) European Clinical Trial 101, we have identified a human leukocyte antigen (HLA)-A2-restricted T cell receptor (TCR) targeting protein tyrosine phosphatase receptor type zeta 1 (PTPRZ1). PTPRZ1 is strongly overexpressed in malignant gliomas, especially GB, and analyses of intratumoral heterogeneity revealed that the level of PTPRZ1 overexpression is strongly associated with cancer stemness. The PTPRZ1 epitope is naturally presented on HLA-A2. MATERIAL AND METHODS INVENT4GB is a German, multicenter, phase 1, first-in-human, first-of-kind dose-escalation window-of-opportunity investigator-initiated trial in recurrent GB, eligible for re-resection, assessing safety and feasibility of therapy with intravenously (iv) and intraventricularly (icv) infused TCR-engineered T cells (TCR-T). FPI is scheduled for 2024. HLA-A*02:01 positive patients will receive one neoadjuvant iv followed by up to three adjuvant icv infusions of PTPRZ1-specific TCR-transgenic autologous T cell therapy (TCR-T-001) with cyclophosphamide- and fludarabine-based lymphodepletion prior to iv infusion. Patient autologous T cells will be engineered by non-integrating nano scaffold matrix attachment region (SMAR) TCR DNA vectors. Icv infusions will be performed via intraventricular catheter implanted during re-resection. Biomarker discovery includes magnetic resonance imaging (MRI) and longitudinal flow cytometry-based immune monitoring of blood and cerebrospinal fluid. Primary endpoints are feasibility and safety (determination of maximum tolerated dose/ MTD), key secondary endpoints are progression-free survival according to the Immunotherapy Response Assessment in Neurooncology (iRANO) criteria. RESULTS TCR-T-001 robustly recognizes target-expressing cells in vitro and is efficacious in preclinical tumor models. Preclinical data and the trial concept will be presented. CONCLUSION INVENT4GB is a first-of-kind TCR-engineered T cell therapy for GB patients.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- P06.05.A INTRACEREBROVENTRICULAR TCR-TRANSGENIC T CELL THERAPY TO TREAT GLIOBLASTOMA (INVENT4GB)
- Date Crossref
- 01/09/2023
- Éditeur
- Oxford University Press (OUP)
- 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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German Cancer Research Center pays non établi dans la noticeStructure de recherche
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Heidelberg University pays non établi dans la noticeUniversité ou école supérieure
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National Center for Tumor Diseases pays non établi dans la noticeOrganisme public
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Goethe University Frankfurt Neurology Clinic pays non établi dans la noticeUniversité ou école supérieure
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University Hospital Frankfurt pays non établi dans la noticeÉtablissement de santé
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Charité - Universitätsmedizin Berlin pays non établi dans la noticeÉtablissement de santé
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University Hospital Heidelberg Neurology Clinic pays non établi dans la noticeÉtablissement de santé
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Trial Center NCT Heidelberg pays non établi dans la noticeInstitution
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Medical Oncology pays non établi dans la noticeInstitution
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Neurosurgery Clinic pays non établi dans la noticeÉtablissement de santé
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Department of Hematology pays non établi dans la noticeInstitution
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University Tübingen Neurology Clinic pays non établi dans la noticeUniversité ou école supérieure
German Cancer Research Center, Heidelberg University et National Center for Tumor Diseases, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.