Actively personalized vaccination trial for newly diagnosed glioblastoma

Autor: 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
Přispěvatelé: Dutoit Vallotton, Valérie, Migliorini, Denis, Dietrich, Pierre-Yves
Jazyk: angličtina
Rok vydání: 2019
Předmět:
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
Zdroj: Nature, 565(7738), 240
Nature, Vol. 565, No 7738 (2019) pp. 240-245
ISSN: 0028-0836
Popis: 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.
Databáze: OpenAIRE
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