New research provides hope for treatment for aggressive brain tumor

Giulia Saronio, Magnus Essand, Tina Sarén, Di Yu, Vendela Parrow and Annette Roos have been involved in the project

Using genetically modified cells, researchers from Uppsala University hope to create a treatment for Glioblastoma, an aggressive brain cancer as of today lacking a cure. “Our ambition is to start clinical studies within four years”, says Magnus Essand, Professor of Gene Therapy.

Immuno-oncology, the method of taking advantage of the body’s own immune system against cancer cells, is an upcoming research field. In 2017 CAR T-cells were approved as treatment for lymphoma and acute lymphocytic leukemia. Now Magnus Essand and Di Yu, researchers at Uppsala University, hope to develop the technique in order to treat Glioblastoma, a highly aggressive brain tumor for which the healthcare system cannot provide a means of therapy.

“The method uses the body’s T-cells and their ability to kill tumor cells. Our ambition is to extract T-cells from the patient, add a chimeric antigen receptor, a so-called CAR, and then reinsert them back into the patient. The CAR will in this case be trained to selectively recognize glioblastoma cells. Development of a CAR T-cell product is a demanding process, one we embarked on several years ago. The results are still looking promising as we now enter the last pre-clinical phase,” says Magnus Essand, Professor of Gene Therapy.

A large step forward was taken in collaboration with the SciLifeLab Drug Discovery and Development Platform (DDD), a national resource that supports Swedish researchers in developing new substances, with the aim of creating future medicines. The joint project CAR T-cells for the treatment of Glioblastoma was initiated in December 2017 and recently resulted in the submission of a patent application for a potential CAR T-binder.

“The research group presented a high-quality project organization, one that our platform has chosen to prioritize through to the end. To use our expertise in the field of antibodies and apply it to CAR T-cells was a new experience for us, one which has given us important knowledge in advanced cell therapy. I am personally very impressed by the research team’s commitment and will follow their continued work with great interest,” says Vendela Parrow, project leader at DDD.

With a focus on flexibility, extensive dialog and efficient problem-solving, the project could be completed by the 3rd June, after two-and-a-half years as a prioritized project at the DDD platform. At a meeting at the Uppsala Biomedical Centre, data and reports were handed over from the platform and both parts stressed the synergy and productivity effects of the collaboration.

“To have access to the expertise and techniques provided by the DDD was critical for us in order to be able to advance our research. The fact that their team has been exceptionally clear in their communication around their progress within the project has made this a very educational time for me,” says Tina Sarén, graduate student at the Department of Immunology, Genetics and Pathology.

An antibody that binds to a tumor antigen expressed by glioblastoma cells was developed and a chimeric antigen receptor (CAR) was created by coupling the antibody to a T-cell receptor. T-cells that carry the CAR will thereby recognize and kill glioblastoma cells.

In the next phase, Magnus Essand and Di Yu will validate the results for continued development before the work to create specific vectors can commence. Keeping the same pace they hope to take the step to clinical trials within the next four years.

“Extremely few breakthroughs have been made around treating Glioblastoma. The tumors give rise to severe symptoms and the average survival expectancy after a diagnosis is only slightly above one year. Creating a cure is still far off, but I hope that within the foreseeable future we can offer a therapy that lengthens as well as improves the quality of life for Glioblastoma patients,” says Magnus Essand.

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