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Actively personalized vaccination trial for newly diagnosed glioblastoma

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Hilf, N, Kuttruff-Coqui, S, Frenzel, K, Bukur, V, Stevanović, S, Gouttefangeas, C, Platten, M, Tabatabai, G, Dutoit, V, van der Burg, SH, Thor Straten, P, Martínez-Ricarte, F, Ponsati, B, Okada, H, Lassen, U, Admon, A, Ottensmeier, CH, Ulges, A, Kreiter, S, von Deimling, A, Skardelly, M, Migliorini, D, Kroep, JR, Idorn, M, Rodon, J, Piró, J, Poulsen, HS, Shraibman, B, McCann, K, Mendrzyk, R, Löwer, M, Stieglbauer, M, Britten, CM, Capper, D, Welters, MJP, Sahuquillo, J, Kiesel, K, Derhovanessian, E, Rusch, E, Bunse, L, Song, C, Heesch, S, Wagner, C, Kemmer-Brück, A, Ludwig, J, Castle, JC, Schoor, O, Tadmor, AD, Green, E, Fritsche, J, Meyer, M, Pawlowski, N, Dorner, S, Hoffgaard, F, Rössler, B, Maurer, D, Weinschenk, T, Reinhardt, C, Huber, C, Rammensee, H-G, Singh-Jasuja, H, Sahin, U, Dietrich, P-Y & Wick, W 2019, 'Actively personalized vaccination trial for newly diagnosed glioblastoma' Nature, vol. 565, no. 7738, pp. 240-245. https://doi.org/10.1038/s41586-018-0810-y

APA

Hilf, N., Kuttruff-Coqui, S., Frenzel, K., Bukur, V., Stevanović, S., Gouttefangeas, C., ... Wick, W. (2019). Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature, 565(7738), 240-245. https://doi.org/10.1038/s41586-018-0810-y

CBE

Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanović S, Gouttefangeas C, Platten M, Tabatabai G, Dutoit V, van der Burg SH, Thor Straten P, Martínez-Ricarte F, Ponsati B, Okada H, Lassen U, Admon A, Ottensmeier CH, Ulges A, Kreiter S, von Deimling A, Skardelly M, Migliorini D, Kroep JR, Idorn M, Rodon J, Piró J, Poulsen HS, Shraibman B, McCann K, Mendrzyk R, Löwer M, Stieglbauer M, Britten CM, Capper D, Welters MJP, Sahuquillo J, Kiesel K, Derhovanessian E, Rusch E, Bunse L, Song C, Heesch S, Wagner C, Kemmer-Brück A, Ludwig J, Castle JC, Schoor O, Tadmor AD, Green E, Fritsche J, Meyer M, Pawlowski N, Dorner S, Hoffgaard F, Rössler B, Maurer D, Weinschenk T, Reinhardt C, Huber C, Rammensee H-G, Singh-Jasuja H, Sahin U, Dietrich P-Y, Wick W. 2019. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 565(7738):240-245. https://doi.org/10.1038/s41586-018-0810-y

MLA

Vancouver

Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanović S, Gouttefangeas C et al. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 2019 Jan;565(7738):240-245. https://doi.org/10.1038/s41586-018-0810-y

Author

Hilf, Norbert ; Kuttruff-Coqui, Sabrina ; Frenzel, Katrin ; Bukur, Valesca ; Stevanović, Stefan ; Gouttefangeas, Cécile ; Platten, Michael ; Tabatabai, Ghazaleh ; Dutoit, Valerie ; van der Burg, Sjoerd H ; Thor Straten, Per ; Martínez-Ricarte, Francisco ; Ponsati, Berta ; Okada, Hideho ; Lassen, Ulrik ; Admon, Arie ; Ottensmeier, Christian H ; Ulges, Alexander ; Kreiter, Sebastian ; von Deimling, Andreas ; Skardelly, Marco ; Migliorini, Denis ; Kroep, Judith R ; Idorn, Manja ; Rodon, Jordi ; Piró, Jordi ; Poulsen, Hans S ; Shraibman, Bracha ; McCann, Katy ; Mendrzyk, Regina ; Löwer, Martin ; Stieglbauer, Monika ; Britten, Cedrik M ; Capper, David ; Welters, Marij J P ; Sahuquillo, Juan ; Kiesel, Katharina ; Derhovanessian, Evelyna ; Rusch, Elisa ; Bunse, Lukas ; Song, Colette ; Heesch, Sandra ; Wagner, Claudia ; Kemmer-Brück, Alexandra ; Ludwig, Jörg ; Castle, John C ; Schoor, Oliver ; Tadmor, Arbel D ; Green, Edward ; Fritsche, Jens ; Meyer, Miriam ; Pawlowski, Nina ; Dorner, Sonja ; Hoffgaard, Franziska ; Rössler, Bernhard ; Maurer, Dominik ; Weinschenk, Toni ; Reinhardt, Carsten ; Huber, Christoph ; Rammensee, Hans-Georg ; Singh-Jasuja, Harpreet ; Sahin, Ugur ; Dietrich, Pierre-Yves ; Wick, Wolfgang. / Actively personalized vaccination trial for newly diagnosed glioblastoma. In: Nature. 2019 ; Vol. 565, No. 7738. pp. 240-245.

Bibtex

@article{b88bc8c7384b45369e71dbee24d98132,
title = "Actively personalized vaccination trial for 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.",
author = "Norbert Hilf and Sabrina Kuttruff-Coqui and Katrin Frenzel and Valesca Bukur and Stefan Stevanović and C{\'e}cile Gouttefangeas and Michael Platten and Ghazaleh Tabatabai and Valerie Dutoit and {van der Burg}, {Sjoerd H} and {Thor Straten}, Per and Francisco Mart{\'i}nez-Ricarte and Berta Ponsati and Hideho Okada and Ulrik Lassen and Arie Admon and Ottensmeier, {Christian H} and Alexander Ulges and Sebastian Kreiter and {von Deimling}, Andreas and Marco Skardelly and Denis Migliorini and Kroep, {Judith R} and Manja Idorn and Jordi Rodon and Jordi Pir{\'o} and Poulsen, {Hans S} and Bracha Shraibman and Katy McCann and Regina Mendrzyk and Martin L{\"o}wer and Monika Stieglbauer and Britten, {Cedrik M} and David Capper and Welters, {Marij J P} and Juan Sahuquillo and Katharina Kiesel and Evelyna Derhovanessian and Elisa Rusch and Lukas Bunse and Colette Song and Sandra Heesch and Claudia Wagner and Alexandra Kemmer-Br{\"u}ck and J{\"o}rg Ludwig and Castle, {John C} and Oliver Schoor and Tadmor, {Arbel D} and Edward Green and Jens Fritsche and Miriam Meyer and Nina Pawlowski and Sonja Dorner and Franziska Hoffgaard and Bernhard R{\"o}ssler and Dominik Maurer and Toni Weinschenk and Carsten Reinhardt and Christoph Huber and Hans-Georg Rammensee and Harpreet Singh-Jasuja and Ugur Sahin and Pierre-Yves Dietrich and Wolfgang Wick",
year = "2019",
month = "1",
doi = "10.1038/s41586-018-0810-y",
language = "English",
volume = "565",
pages = "240--245",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7738",

}

RIS

TY - JOUR

T1 - Actively personalized vaccination trial for newly diagnosed glioblastoma

AU - Hilf, Norbert

AU - Kuttruff-Coqui, Sabrina

AU - Frenzel, Katrin

AU - Bukur, Valesca

AU - Stevanović, Stefan

AU - Gouttefangeas, Cécile

AU - Platten, Michael

AU - Tabatabai, Ghazaleh

AU - Dutoit, Valerie

AU - van der Burg, Sjoerd H

AU - Thor Straten, Per

AU - Martínez-Ricarte, Francisco

AU - Ponsati, Berta

AU - Okada, Hideho

AU - Lassen, Ulrik

AU - Admon, Arie

AU - Ottensmeier, Christian H

AU - Ulges, Alexander

AU - Kreiter, Sebastian

AU - von Deimling, Andreas

AU - Skardelly, Marco

AU - Migliorini, Denis

AU - Kroep, Judith R

AU - Idorn, Manja

AU - Rodon, Jordi

AU - Piró, Jordi

AU - Poulsen, Hans S

AU - Shraibman, Bracha

AU - McCann, Katy

AU - Mendrzyk, Regina

AU - Löwer, Martin

AU - Stieglbauer, Monika

AU - Britten, Cedrik M

AU - Capper, David

AU - Welters, Marij J P

AU - Sahuquillo, Juan

AU - Kiesel, Katharina

AU - Derhovanessian, Evelyna

AU - Rusch, Elisa

AU - Bunse, Lukas

AU - Song, Colette

AU - Heesch, Sandra

AU - Wagner, Claudia

AU - Kemmer-Brück, Alexandra

AU - Ludwig, Jörg

AU - Castle, John C

AU - Schoor, Oliver

AU - Tadmor, Arbel D

AU - Green, Edward

AU - Fritsche, Jens

AU - Meyer, Miriam

AU - Pawlowski, Nina

AU - Dorner, Sonja

AU - Hoffgaard, Franziska

AU - Rössler, Bernhard

AU - Maurer, Dominik

AU - Weinschenk, Toni

AU - Reinhardt, Carsten

AU - Huber, Christoph

AU - Rammensee, Hans-Georg

AU - Singh-Jasuja, Harpreet

AU - Sahin, Ugur

AU - Dietrich, Pierre-Yves

AU - Wick, Wolfgang

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41586-018-0810-y

DO - 10.1038/s41586-018-0810-y

M3 - Journal article

VL - 565

SP - 240

EP - 245

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7738

ER -

ID: 56272044