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Clinical Trials of Cancer Immunotherapies

Abstract A020: Immunomonitoring for actively personalized peptide vaccines (APVACs) during immunotherapeutic treatment of glioblastoma

Alexander Ulges, Norbert Hilf, Wolfgang Wick, Michael Platten, Pierre-Yves Dietrich, Katrin Frenzel, Arie Admon, Sjoerd S.H. van der Burg, Andreas von Deimling, Per thor Straten, Cecile Gouttefangeas, Judith R. Kroep, Francisco Martínez-Ricarte, Hideo Okada, Christian H. Ottensmeier, Berta Ponsati, Hans S. Poulsen, Stefan Stevanovic, Ghazaleh Tabatabai, Hans-Georg Rammensee, Ugur Sahin, Dominik Maurer and Regina Mendrzyk
Alexander Ulges
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Norbert Hilf
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Wolfgang Wick
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Michael Platten
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Pierre-Yves Dietrich
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Katrin Frenzel
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Arie Admon
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Sjoerd S.H. van der Burg
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Andreas von Deimling
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Per thor Straten
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Cecile Gouttefangeas
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Judith R. Kroep
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Francisco Martínez-Ricarte
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Hideo Okada
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Christian H. Ottensmeier
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Berta Ponsati
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Hans S. Poulsen
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Stefan Stevanovic
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Ghazaleh Tabatabai
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Hans-Georg Rammensee
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Ugur Sahin
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Dominik Maurer
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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Regina Mendrzyk
Immatics Biotechnologies GmbH, Tübingen, Germany; University Hospital Heidelberg, Heidelberg, Germany; Université de Genève, Genève, Switzerland; BioNTech AG, Mainz, Germany; Technion - Israel Institute of Technology, Haifa, Israel; Leiden University Medical Center, Rotterdam, The Netherlands; University Hospital Herlev, Herlev, Denmark; Leiden University Medical Center, Leiden, The Netherlands; Vall d’Hebron University Hospital, Barcelona, Spain; University of California San Francisco, San Francisco, CA; University of Southampton, Southampton, United Kingdom; BCN Peptides S.A., Barcelona, Spain; Ringhospitalet, Copenhagen, Denmark; University of Tübingen, Tübingen, Germany.
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DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A020 Published February 2019
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Abstracts: Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 30 - October 3, 2018; New York, NY

Abstract

Cancer immunotherapy to gliomas has so far failed to show encouraging results, as gliomas are rarely mutated and show various mechanisms of immune escape. To improve therapy to these type of cancer, the Glioma Actively Personalized Vaccine Consortium (GAPVAC) integrated a highly personalized peptide vaccine approach into glioblastoma standard of care treatment combining neoepitope and nonmutated tumor antigens to exploit the full repertoire of tumor antigens. In this phase I clinical trial fifteen patients received two different types of personalized peptide vaccines (APVAC1 and APVAC2), that were selected based on transcriptome, immunopeptidome and mutational analysis of the patient’s individual tumors. While APVAC1 vaccines were composed of nonmutated tumor antigens selected in a warehouse-based approach, APVAC2 vaccines primarily targeted neoepitopes. Both vaccines were used in combination with poly-ICLC and GM-CSF as adjuvants and demonstrated expected safety profile and outstanding Immunogenicity. Immunomonitoring of APVAC1 peptides was carried out using a combinatorial ex vivo Class I 2D multimer (2DMM) and Class II intracellular cytokine staining (ICS) assay with an outstanding sensitivity to detect even one peptide-specific cell in one million of CD4 or CD8 T-cells. Nonmutated APVAC1 class I peptides showed induction of persistent CD8 T-cell responses, mainly consisting of a highly favorable central memory phenotype (CM). Furthermore, APVAC1 class II peptides demonstrated induction of polyfunctional CD4 T-cells predominantly of a type 1 T helper cell (TH1) phenotype. Notably, an APVAC1 class II specific T-cell response was detected in tumor-infiltrating lymphocyte (TIL) fraction obtained from resection of one patient. On the other side, immune responses to APVAC2 peptides were analyzed using a pan-ICS assay including a single in vitro sensitization step to analyze a broad array of cytokines produced by CD4 T helper (TH) cells and CD8 CTLs in parallel. APVAC2 peptides showed excellent immunogenicity and induced potent and multifunctional CD4 T-cell responses, mostly of a TH1 phenotype that often concurred with CTL responses. Furthermore, the induction of APVAC1-specific CD8 memory cells, as a marker for the potency of the vaccine-induced immune responses, reversely correlated with the baseline frequencies of regulatory T-cells (Treg). Taken together, actively personalized peptide vaccines (APVACs) were highly immunogenic and induced sustained responses of a highly favorable CD4 and CD8 T-cell phenotype. The vaccination showed the expected safety profile and the approach was feasible, even in this highly individualized setting. Therefore, the APVAC vaccination approach clearly represents a step forward on the path to bring the benefit of immunotherapy to glioblastoma patients.

Citation Format: Alexander Ulges, Norbert Hilf, Wolfgang Wick, Michael Platten, Pierre-Yves Dietrich, Katrin Frenzel, Arie Admon, Sjoerd S.H. van der Burg, Andreas von Deimling, Per thor Straten, Cecile Gouttefangeas, Judith R. Kroep, Francisco Martínez-Ricarte, Hideo Okada, Christian H. Ottensmeier, Berta Ponsati, Hans S. Poulsen, Stefan Stevanovic, Ghazaleh Tabatabai, Hans-Georg Rammensee, Ugur Sahin, Dominik Maurer, Regina Mendrzyk. Immunomonitoring for actively personalized peptide vaccines (APVACs) during immunotherapeutic treatment of glioblastoma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A020.

  • ©2019 American Association for Cancer Research.
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Cancer Immunology Research: 7 (2 Supplement)
February 2019
Volume 7, Issue 2 Supplement
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Abstract A020: Immunomonitoring for actively personalized peptide vaccines (APVACs) during immunotherapeutic treatment of glioblastoma
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Abstract A020: Immunomonitoring for actively personalized peptide vaccines (APVACs) during immunotherapeutic treatment of glioblastoma
Alexander Ulges, Norbert Hilf, Wolfgang Wick, Michael Platten, Pierre-Yves Dietrich, Katrin Frenzel, Arie Admon, Sjoerd S.H. van der Burg, Andreas von Deimling, Per thor Straten, Cecile Gouttefangeas, Judith R. Kroep, Francisco Martínez-Ricarte, Hideo Okada, Christian H. Ottensmeier, Berta Ponsati, Hans S. Poulsen, Stefan Stevanovic, Ghazaleh Tabatabai, Hans-Georg Rammensee, Ugur Sahin, Dominik Maurer and Regina Mendrzyk
Cancer Immunol Res February 1 2019 (7) (2 Supplement) A020; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A020

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Abstract A020: Immunomonitoring for actively personalized peptide vaccines (APVACs) during immunotherapeutic treatment of glioblastoma
Alexander Ulges, Norbert Hilf, Wolfgang Wick, Michael Platten, Pierre-Yves Dietrich, Katrin Frenzel, Arie Admon, Sjoerd S.H. van der Burg, Andreas von Deimling, Per thor Straten, Cecile Gouttefangeas, Judith R. Kroep, Francisco Martínez-Ricarte, Hideo Okada, Christian H. Ottensmeier, Berta Ponsati, Hans S. Poulsen, Stefan Stevanovic, Ghazaleh Tabatabai, Hans-Georg Rammensee, Ugur Sahin, Dominik Maurer and Regina Mendrzyk
Cancer Immunol Res February 1 2019 (7) (2 Supplement) A020; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A020
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Clinical Trials of Cancer Immunotherapies

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Clinical Trials of Cancer Immunotherapies: Poster Presentations - Proffered Abstracts

  • Abstract A007: Comparison of pretreatment conditioning on efficacy in two cohorts of a pilot study of genetically engineered NY-ESO-1c259T-cells in patients with synovial sarcoma
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