Collaboration to develop new glioblastoma combination therapy nets €1.06M

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glioblastoma oncolytic virus transgene 2

Dutch biotech CimCure B.V., French biotech company Covalab, Amsterdam UMC (The Netherlands) and the University of Zurich (Switzerland), have received a €1.06M ($1.08M) grant from EUREKA Eurostars.

With a total budget of €2.24M ($2.28M), including investments from the partners, the project aims to develop a new treatment against glioblastoma. CimCure is the lead coordinator of the project.

Glioblastoma (GBM) is one of the most complex, deadly and treatment-resistant cancers, accounting for almost half of all primary malignant brain tumors. The consortium will develop a combination therapy using CimCure’s iBoost vaccines and CAR-T cells against GBM. The project, ‘Optimal Synergistic Immunotherapy Strategy (OpSIS)’, will take place over 36 months in academic research labs in the Netherlands and Switzerland, as well as in the Covalab and CimCure facilities.

OpSIS aims to deliver preclinical proof of concept for a novel combination of immunotherapy treatment for GBM, to then provide a validation for translation of this strategy in GBM patients. This project strives to demonstrate the efficacy, long-term persistence and synergistic ability of combining GMB-targeting CAR-T cells with tumor vasculature-targeting vaccines.

Initial study 

The project is based on an initial study conducted by Amsterdam UMC and the Medical Center for Animals (MCD), where a vaccine against bone cancer was successful in an efficacy study in client-owned dogs. The vaccine-based immunotherapy developed by the team of Arjan Griffioen, professor of experimental oncology at Amsterdam UMC was licensed to CimCure. It has shown to be highly effective and safe, both in murine animal models and in an efficacy study in dogs with spontaneous bladder cancer. 

In May 2022, some of the research results which underlie this innovation were published in Nature Communications (Van Beijnum et al, 2022). Utilizing CimCure’s iBoost vaccine-based cancer immunotherapy, the project aims to replicate the results of the Amsterdam UMC trials in humans.

Antibody development is crucial for the advancement of these vaccines and CAR-T cells. Covalab, as a developer of custom antibodies projects, will produce monoclonal antibodies for vascular targets identified by Amsterdam UMC and will help CimCure to study passive immunization. Additionally, Covalab will develop full-length and antibody fragments, to be used for CAR-T cells. This novel approach to antibody production by using DNA immunization is vital to the project.

“We are excited to bring our extensive expertise in antibody engineering to the OpSIS project. Additionally, our platforms in molecular biology, immunology and bioproduction will support the preclinical validation of therapeutic molecules and we can use our know-how in anticancer immunotherapy for this unique combination therapy project in oncology,” said Saïd El Alaoui, CEO and founder of Covalab. 

“Covalab has already received a Eurostars grant in 2017 for the validation of its patented technology CovIsoLink in the field of ADC (antibody drug conjugates), a new and innovative technology for cancer therapy, proving its track record in taking on collaborative, international projects.”

Developing libraries

The new Covalab platforms in the field of phage display and DNA immunization allow the company to develop different libraries of antibodies and fragments (scFv, VHH, Fab, etc.) from natural (naïve) and immune sources with large sequence diversity. Thanks to the preliminary construction of proprietary libraries against some therapeutic targets, Covalab can select antibody fragments with high specificity and affinity which may prove to be valuable therapeutic molecules.

“The Eurostars funding of OpSIS provides a unique opportunity to test our iBoost vaccines in combination with other immunotherapy approaches. We see an important innovation in testing this combination strategy in glioblastoma, a disease with a dismal clinical outcome. The collaboration with Covalab, the University of Zurich and Amsterdam UMC is unique and promises major achievements,” said Diederik Engbersen, CEO at CimCure.

“Immunotherapy for brain tumors has been a major research focus at the University of Zurich. We are delighted to join forces with colleagues from the Netherlands and France, OpSIS will enable the development of novel treatment approaches by combining innovative immunotherapeutic strategies, to be explored in various clinically relevant models,” said Patrick Roth, University Hospital Zurich, Department of Neurology.

The OpSIS group will optimize its innovative therapeutic approach by determining the most suitable tumor targets and vaccination strategies. The end goal of the project is to have the combination therapy ready to enter regulatory procedures for testing patients.

EUREKA Eurostars

Eurostars is a part of the Horizon Europe program that supports SMEs and project partners (universities, research organizations and other types of organizations) by funding international collaborative R&D and innovation projects. Eurostars is run by EUREKA, an intergovernmental network, which involves 37 countries. 

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