A project supported by a $7.7 million European Union Framework 7 (EU FP7) program grant to develop a novel class of therapeutic cancer vaccines is underway.

The Glioma Actively Personalized VAccine Consortium (GAPVAC) is the first E.U.-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 expertise in cancer vaccine development. The consortium will be led by Germany-based companies immatics Biotechnologies (coordinator) and BioNTech (vice coordinator).

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 tumor and immune system. 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 unmet medical need in glioblastoma, a form of brain cancer with poor prognosis, for which the limited treatments available 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. 

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 I 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 trial will be led by Prof. Dr. Wolfgang Wick, chief investigator, University of Heidelberg, and co-led by Prof. Dr. Pierre-Yves Dietrich, University of Geneva. 

immatics will use its antigen discovery engine XPRESIDENT to generate 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 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 tumor mutations and generate a blueprint for the personalized vaccine that will include patient-specific tumor mutated peptides.

BioNTech has demonstrated that the integrated use of NGS for genome-wide mutation identification followed by mutation-targeting vaccination is feasible and leads to tumor control in preclinical models. The APVAC “on-demand” manufacturing will be performed by the GMP-unit at the Department of Immunology, University of Tuebingen. The peptide warehouse will be manufactured by BCN Peptides in Spain, an enterprise focused on peptide synthesis for clinical use.

In addition, 10 academic partners from Europe and the U.S. 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 Center, Universities Hospital Geneva, Universities Hospital Heidelberg, Herlev Hospital/Rigshospitalet (Denmark), Leiden University Medical Center (The Netherlands), University of Pittsburgh Cancer Institute, University Southampton (U.K.), Technion (Israel) and Vall d’Hebron University Hospital (Spain).

The trial will be accompanied by a biomarker program led by the Association of Cancer Immunotherapy (CIMT), a nonprofit 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.