Researchers conducted first trial of personalized vaccine for brain cancer

24 December 2018

GMP News

Clinical study demonstrates proof-of-concept of the Glioma Actively Personalized Vaccine Consortium (GAPVAC) approach in a pioneering multi-center, multi-national study co-funded by the European Union.

The prospect of an actively personalized approach to the treatment of glioblastoma has  moved a step closer with the recent publication in Nature of favorable data from the phase 1 study GAPVAC-101, testing a novel therapeutic concept tailored to specific characteristics of patients’ individual tumors and immune systems. For the first time, the feasibility of such a highly personalized form of immunotherapy has been exemplified in a multi-center, multi-national clinical setting.

The Glioma Actively Personalized Vaccine Consortium (GAPVAC) approach is a highly personalized method being progressed through the GAPVAC-101 first-in-human clinical trial by a European Union-funded consortium, led by Immatics Biotechnologies GmbH(Tuebingen, Germany) and BioNTech AG (Mainz, Germany).

Patients in this study were treated at six European centers: The University Hospital of Heidelberg (Germany), the University Hospital of Tuebingen (Germany), the Geneva University Hospital (Switzerland), the Leiden University Medical Center (The Netherlands), the Rigshospitalet (Copenhagen, Denmark), and the Vall d’Hebron University Hospital (Barcelona, Spain). Furthermore, the Department of Immunology, University of Tuebingen (led by Prof. Hans-Georg Rammensee), BCN Peptides (Barcelona, Spain), the Association of Cancer Immunotherapy (CIMT), the University of California San Francisco (US), the University Southampton (UK), and the Technion-Israel Institute of Technology (Haifa, Israel) participated in the study involving a pioneering concept, complex manufacturing, logistics and various biomarker analyses.

GAPVAC was launched in 2013 being the first clinical trial at that time designed to create, manufacture and develop actively personalized vaccines (APVACs) tailored to the individual characteristics of the patient’s tumor and immune system. It is based on combining latest state- of-the-art technologies, including next-generation sequencing (NGS), high-sensitivity mass spectrometry and innovative immunomonitoring approaches to generate an optimal therapy for the individual patient.

The GAPVAC-101 trial was led by Prof. Dr. Wolfgang Wick (University of Heidelberg) and Prof. Dr. Pierre-Yves Dietrich (University of Geneva).

Immatics Biotechnologies used its unique antigen discovery engine XPRESIDENT in collaboration with the University of Geneva, University of Heidelberg and the University of Tuebingen to generate a pre-manufactured warehouse of tumor-associated peptides (TUMAPs) from which the most suitable targets for each patient were selected based on transcriptomic, immunogenic and peptidomic analysis to create the first of two APVACs applied to the patient.

BioNTech used its next-generation sequencing (NGS) expertise to identify immunogenic tumor mutations and to generate a blueprint for the personalized vaccine that included patient- specific tumor mutated peptides. Previously, BioNTech has demonstrated that the integrated use of NGS for mutation identification followed by mutation-targeting vaccination is feasible and led to tumor control in pre-clinical models.

The APVAC “on-demand” manufacturing was performed by the GMP Unit, led by Prof. Dr. Stefan Stevanovic, at the Department of Immunology, led by Prof. Dr. Hans-Georg Rammensee (University of Tuebingen). Prof. Hans-Georg Rammensee was among the first to create the vision of fully personalized vaccination back in 2000. The peptide warehouse was manufactured by BCN Peptides in Spain, an enterprise focused on peptide synthesis for clinical use. In addition, nine academic partners from Europe and the US are part of the consortium to apply the APVACs to their patients as well as contributing to the project with their own research.

The clinical trial is being accompanied by an extensive biomarker program led by the Association of Cancer Immunotherapy (CIMT), a non-profit organization dedicated to the advancement of cancer vaccines, and Immatics to confirm the mechanism-of-action and to identify biomarker signature candidates predicting which patients are most likely to benefit from treatment with APVACs.

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