Actively personalized vaccination trial for newly diagnosed glioblastoma
Norbert Hilf,Sabrina Kuttruff-Coqui,Katrin Frenzel,Valesca Bukur,Stefan Stevanovic,Stefan Stevanovic,Cécile Gouttefangeas,Cécile Gouttefangeas,Michael Platten,Michael Platten,Ghazaleh Tabatabai,Ghazaleh Tabatabai,Valérie Dutoit,Sjoerd H. van der Burg,Per thor Straten,Per thor Straten,Francisco Martínez-Ricarte,Berta Ponsati,Hideho Okada,Ulrik Lassen,Arie Admon,Christian H. Ottensmeier,Alexander Ulges,Sebastian Kreiter,Andreas von Deimling,Andreas von Deimling,Marco Skardelly,Denis Migliorini,Judith R. Kroep,Manja Idorn,Manja Idorn,Jordi Rodon,Jordi Rodon,Jordi Piro,Hans Skovgaard Poulsen,Bracha Shraibman,Katy J. McCann,Regina Mendrzyk,Martin Löwer,Monika Stieglbauer,Cedrik M. Britten,David Capper,David Capper,David Capper,Marij J. P. Welters,Juan Sahuquillo,Katharina Kiesel,Evelyna Derhovanessian,Elisa Rusch,Lukas Bunse,Lukas Bunse,Colette Song,Sandra Heesch,Claudia Wagner,Alexandra Kemmer-Brück,Jorg Ludwig,John C. Castle,Oliver Schoor,Arbel D. Tadmor,Edward W. Green,Jens Fritsche,Miriam Meyer,Nina Pawlowski,Sonja Dorner,Franziska Hoffgaard,Bernhard Rossler,Dominik Maurer,Toni Weinschenk,Carsten Reinhardt,Christoph Huber,Hans-Georg Rammensee,Hans-Georg Rammensee,Harpreet Singh-Jasuja,Ugur Sahin,Pierre-Yves Dietrich,Wolfgang Wick,Wolfgang Wick +76 more
TLDR
In a phase I trial, highly individualized peptide vaccines against unmutated tumour antigens and neoepitopes elicited sustained responses in CD8+ and CD4+ T cells, respectively, in patients with newly diagnosed glioblastoma.Abstract:
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.read more
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Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions
Patrick Y. Wen,Michael Weller,Eudocia Q. Lee,Brian M. Alexander,Jill S. Barnholtz-Sloan,Floris P. Barthel,Tracy T. Batchelor,Ranjit S. Bindra,Susan M. Chang,E. Antonio Chiocca,Timothy F. Cloughesy,John DeGroot,Evanthia Galanis,Mark R. Gilbert,Monika E. Hegi,Craig Horbinski,Raymond Y. Huang,Andrew B. Lassman,Emilie Le Rhun,Michael Lim,Minesh P. Mehta,Ingo K. Mellinghoff,Giuseppe Minniti,David Nathanson,Michael Platten,Matthias Preusser,Patrick Roth,Marc Sanson,David Schiff,Susan C Short,Martin J B Taphoorn,Joerg C. Tonn,Jonathan Tsang,Roel G.W. Verhaak,Andreas von Deimling,Wolfgang Wick,Gelareh Zadeh,David A. Reardon,Kenneth Aldape,Martin J. van den Bent +39 more
TL;DR: Novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies and viral therapies will be reviewed, as well as the current challenges and future directions for research.
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Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion
TL;DR: In this paper, the authors review the tumour-derived factors modulating DC function, and summarize evidence of immune evasion by means of quantitative modulation or qualitative alteration of the antigen repertoire presented on tumours.
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Mechanisms of immunotherapy resistance: lessons from glioblastoma.
TL;DR: The mechanisms of immunotherapy resistance in GBM are reviewed and how insights into GBM–immune system interactions might inform the next generation of immunotherapeutics for GBM and other resistant pathologies are discussed.
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Neoantigen vaccine: an emerging tumor immunotherapy
Miao Peng,Miao Peng,Yongzhen Mo,Yian Wang,Pan Wu,Yijie Zhang,Fang Xiong,Can Guo,Xu Wu,Xu Wu,Yong Li,Xiaoling Li,Guiyuan Li,Guiyuan Li,Wei Xiong,Wei Xiong,Zhaoyang Zeng,Zhaoyang Zeng +17 more
TL;DR: Tumor vaccines targeting neoantigens mainly include nucleic acid, dendritic cell (DC)-based, tumor cell, and synthetic long peptide (SLP) vaccines, which might achieve better therapeutic effects in the future.
Journal ArticleDOI
Advances in the development of personalized neoantigen-based therapeutic cancer vaccines
Eryn Blass,Patrick A. Ott +1 more
TL;DR: In this article, the authors provide an overview of the complex process that is necessary to generate a personalized neoantigen vaccine, review the types of vaccine-induced T cells that are found within tumours and outline strategies to enhance the T cell responses.
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