An innovative project supported by a €6 million European Union Framework 7 (EU FP7) programme grant to develop a novel class of therapeutic cancer vaccines is now under way.

The Glioma Actively Personalized VAccine Consortium (GAPVAC) is the first EU-funded initiative aimed at clinically developing biomarker-guided actively personalized vaccines (APVACs) to treat cancer patients. The consortium consists of 14 organizations from the biotech industry and academia with cutting-edge expertise in cancer vaccine development. The consortium will be led by immatics biotechnologies GmbH (Coordinator) and BioNTech AG (Vice Coordinator). Both companies are located in Germany and are dedicated to a biomarker-guided approach to fight cancer.

The project: The GAPVAC project is designed to create, manufacture and develop actively personalized vaccines (APVACs) tailored for each patient based on the individual aspects of the patient’s tumour and immune system. The latest technologies, including next-generation sequencing (NGS), high-sensitivity mass spectrometry and innovative immunomonitoring approaches, will be combined to generate an optimal therapy for the individual patient.

GAPVAC will address the high unmet medical need in glioblastoma, an aggressive form of brain cancer with poor prognosis, where the limited treatments available today have minimal effect on overall survival. The project aims to show that APVACs are well tolerated and induce a strong and specific immune response against cancer. Furthermore, the partners will demonstrate that this novel personalized approach is feasible.

The clinical trial: immatics and BioNTech will jointly take this actively personalized approach to immunotherapy into clinical development. At the core of the GAPVAC project is a phase 1 clinical trial which will enroll up to 30 newly diagnosed glioblastoma patients and is expected to start in 2014. Glioblastoma patients will be repetitively immunized with a vaccine specifically prepared for each individual. This actively personalized vaccine will be administered in addition to standard chemotherapy after surgery and initial radiochemotherapy are completed. The clinical trial will be led by chief investigator Prof. Dr. Wolfgang Wick, University of Heidelberg, and co-led by Prof. Dr. Pierre-Yves Dietrich, University of Geneva, both internationally recognized experts in the treatment and immunology of brain cancer.

The partners: immatics will use its unique antigen discovery engine XPRESIDENT to generate a warehouse of tumor-associated peptides (TUMAPs) from which the most suitable for each patient are selected based on transcriptomic and peptidomic analysis to create the first of two APVACs applied to the patient. BioNTech AG will add proprietary glioblastoma-expressed tumor-associated antigens to the peptide warehouse. immatics and BioNTech will use their mass spectrometry and next-generation sequencing (NGS) expertise, respectively, to identify immunogenic tumour mutations and generate a blueprint for the personalized vaccine that will include patient-specific tumour mutated peptides. For the first time, BioNTech has demonstrated that the integrated use of NGS for genome-wide mutation identification (the “mutanome”) followed by mutation-targeting vaccination is feasible and leads to tumour control in pre-clinical models. The APVAC “on-demand” manufacturing will be performed by the GMP-unit at the Department of Immunology (led by Prof. Dr. Hans-Georg Rammensee), University of Tuebingen. The complex peptide warehouse will be manufactured by BCN Peptides in Spain, an enterprise focused on peptide synthesis for clinical use. In addition, ten academic partners from Europe and the US have joined the consortium to apply the APVACs to their patients as well as contributing to the project with their own research. These will be: Eberhard Karls University Tuebingen (Germany), Beatson West of Scotland Cancer Centre (Scotland), Universities Hospital Geneva (Switzerland), Universities Hospital Heidelberg (Germany), Herlev Hospital/ Rigshospitalet (Denmark), Leiden University Medical Centre (The Netherlands), University of Pittsburgh Cancer Institute (US), University Southampton (UK), Technion (Israel) and Vall d’Hebron University Hospital (Spain).

The clinical trial will be 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. CIMT will also act as the dissemination platform and will contribute to the biomarker program and regulatory approach through its working parties.

Dr. Harpreet Singh, Chief Scientific Officer of immatics and Coordinator of the GAPVAC consortium, said: “GAPVAC represents an exciting step forward as the first project exploring actively personalized therapeutic cancer vaccines at a European level. Unlike other approaches, this consortium is looking at the specific characteristics of each patient’s disease. If successful, this novel approach could create a completely new way to treat cancer. Such a unique approach is only possible by combining a variety of the latest technological innovations and by joining forces with superb biotechnology companies and academic institutions – by partners who share a dedication for the personalization of therapy for the benefit of cancer patients.”