Actively personalized vaccination trial for newly diagnosed glioblastoma
| العنوان: | Actively personalized vaccination trial for newly diagnosed glioblastoma |
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| المؤلفون: | Marij J. P. Welters, Dominik Maurer, Ulrik Lassen, Martin Löwer, Bernhard Rossler, Ugur Sahin, Andreas von Deimling, Toni Weinschenk, Christian H. Ottensmeier, Elisa Rusch, Colette Song, Valérie Dutoit, Jordi Rodon, Norbert Hilf, Hans Skovgaard Poulsen, Nina Pawlowski, Francisco Martínez-Ricarte, Judith R. Kroep, Juan Sahuquillo, Claudia Wagner, Edward W. Green, Sonja Dorner, Cedrik M. Britten, Franziska Hoffgaard, Jens Fritsche, Ghazaleh Tabatabai, Stefan Stevanovic, Harpreet Singh-Jasuja, Marco Skardelly, Sabrina Kuttruff-Coqui, Hans-Georg Rammensee, Katharina Kiesel, Alexander Ulges, Carsten Reinhardt, Michael Platten, Alexandra Kemmer-Brück, Bracha Shraibman, Denis Migliorini, Sebastian Kreiter, Jordi Piro, Oliver Schoor, Valesca Bukur, Katrin Frenzel, Berta Ponsati, David Capper, Jorg Ludwig, Monika Stieglbauer, Regina Mendrzyk, Miriam Meyer, Sjoerd H. van der Burg, Evelyna Derhovanessian, Pierre-Yves Dietrich, Arie Admon, Arbel D. Tadmor, Manja Idorn, Wolfgang Wick, Hideho Okada, Per thor Straten, Sandra Heesch, Lukas Bunse, Christoph Huber, Katy J. McCann, Cécile Gouttefangeas, John C. Castle |
| المساهمون: | Dutoit Vallotton, Valérie, Migliorini, Denis, Dietrich, Pierre-Yves |
| المصدر: | Nature, 565(7738), 240 Nature, Vol. 565, No 7738 (2019) pp. 240-245 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, T-Lymphocytes Helper-Inducer/immunology, T cell, Antigens Neoplasm/immunology, Epitopes, T-Lymphocyte, Human leukocyte antigen, CD8-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines, Epitopes, 03 medical and health sciences, 0302 clinical medicine, Immune system, Glioblastoma/diagnosis/immunology/therapy, Antigen, Antigens, Neoplasm, Glioma, medicine, Humans, Precision Medicine, Aged, ddc:616, Cancer Vaccines/immunology/therapeutic use, HLA-A Antigens/immunology, Multidisciplinary, HLA-A Antigens, business.industry, T-Lymphocyte/immunology, Immunogenicity, T-Lymphocytes, Helper-Inducer, Precision Medicine/methods, Middle Aged, medicine.disease, Vaccination, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Immunologic Memory/immunology, 030220 oncology & carcinogenesis, Cancer research, Female, Glioblastoma, business, Immunologic Memory, CD8 |
| الوصف: | Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors1,2. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential3. There is limited intratumoural infiltration of immune cells4 in glioblastoma and these tumours contain only 30–50 non-synonymous mutations5. Exploitation of the full repertoire of tumour antigens—that is, both unmutated antigens and neoepitopes—may offer more effective immunotherapies, especially for tumours with a low mutational load. Here, in the phase I trial GAPVAC-101 of the Glioma Actively Personalized Vaccine Consortium (GAPVAC), we integrated highly individualized vaccinations with both types of tumour antigens into standard care to optimally exploit the limited target space for patients with newly diagnosed glioblastoma. Fifteen patients with glioblastomas positive for human leukocyte antigen (HLA)-A*02:01 or HLA-A*24:02 were treated with a vaccine (APVAC1) derived from a premanufactured library of unmutated antigens followed by treatment with APVAC2, which preferentially targeted neoepitopes. Personalization was based on mutations and analyses of the transcriptomes and immunopeptidomes of the individual tumours. The GAPVAC approach was feasible and vaccines that had poly-ICLC (polyriboinosinic-polyribocytidylic acid-poly-l-lysine carboxymethylcellulose) and granulocyte–macrophage colony-stimulating factor as adjuvants displayed favourable safety and strong immunogenicity. Unmutated APVAC1 antigens elicited sustained responses of central memory CD8+ T cells. APVAC2 induced predominantly CD4+ T cell responses of T helper 1 type against predicted neoepitopes. |
| وصف الملف: | text |
| اللغة: | English |
| تدمد: | 0028-0836 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::11b11cf9d2f3e8456103640b3a57a625 https://hdl.handle.net/1887/119498 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....11b11cf9d2f3e8456103640b3a57a625 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 00280836 |
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