The European Research Council (ERC) supports visionary, ground-breaking research projects with its "Advanced Grants". This year, the Council awarded the prestigious funding to two researchers at the German Cancer Research Center (DKFZ): Neuroscientist Hannah Monyer, DKFZ and Heidelberg University Hospital, wants to find new explanations for the development of neurodegenerative diseases. Neurologist Michael Platten, DKFZ and University Medical Center Mannheim, will use the ERC funding to develop and test personalized cellular immunotherapies against malignant brain tumors.
The European Research Council promotes basic research in order to advance particularly forward-looking projects and open up new interdisciplinary fields of knowledge. Each year, the Council announces "ERC Advanced Grants" for outstanding researchers in Europe, which are awarded in a highly competitive process. This year, two DKFZ researchers, Hannah Monyer and Michael Platten, have been awarded the particularly prestigious ERC grants.
New approach to the treatment of neurodegenerative diseases
The hippocampus is an area of the cerebrum in which new memory is created. The activity of the hippocampus is controlled by a small region of the brain known as the septum. Certain inhibitory neurons of the septum are considered "pacemaker cells": they extend into the structures of the hippocampus, where they synchronize the activity of neuronal ensembles and enable cognitive performance.
Hannah Monyer has evidence that the septal neurons are associated with the development of neurodegenerative diseases. If these neurons are damaged, spatial and episodic memory (i.e. what, when, where) are impaired. In various animal models of neurodegenerative diseases, an increased sensitivity of the septal neurons has been observed. They are considered to be very susceptible to disturbance because they fire at a high rate and are therefore extremely hungry for energy. There are hints that damage to the energy-producing mitochondria is responsible for this susceptibility.
In her project, funded by the ERC with two million euros over four years, Monyer wants to investigate how a loss of function of the septal neurons affects memory formation in the downstream hippocampus and which cellular mechanisms are underlying this. What makes the septal neurons so vulnerable? Is it really mitochondrial defects? Monyer and her team want to find out what role these special neurons play in the symptoms in the early stages of neurodegenerative diseases and whether they could therefore represent a potential new target for therapeutic interventions.
Hannah Monyer heads the Clinical Neurobiology Division, which is based at both the DKFZ and Heidelberg University Hospital. The neuroscientist has already received numerous awards, including the Leibniz Prize in 2004. In 1999, she received the Order of Merit of the Federal Republic of Germany. The ERC had already awarded her an Advanced Grant in 2010.
Personalized cellular immunotherapies against malignant brain tumors
Malignant brain tumors are usually incurable diseases that often cannot be completely removed surgically. Cellular immunotherapies that specifically target such brain tumors could be a promising treatment alternative. Michael Platten wants to use artificial intelligence to advance personalized cellular immunotherapies against malignant brain tumours in a project funded by the ERC with 2.5 million euros over five years.
Platten and his team recently invented an innovative approach for the development of cellular immunotherapies: They first isolate T cells from patients' tumor tissue - without knowing the specificity of their T cell receptors. An AI model trained on the genetic sequence data of these T cells can predict which T cell receptors recognize the cancer. This classifier, called "predicTCR ", identifies tumor-reactive T cells with an accuracy of over 90 percent.
The researchers now want to use predicTCR to investigate the genetic programs of tumor-reactive T cells isolated from brain tumors and use these programs to improve the anti-tumor activity of the immune cells.
To obtain therapeutic T cells, the genes of T cell receptors with strong activity against glioblastoma cells must be isolated and transferred to donor T cells. The resulting T-cell receptor transgenic T-cells will then be further tested and prepared for clinical application.
Michael Platten heads the Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology and is spokesperson for the Research Program Immunology, Infection and Cancer at the DKFZ and Medical Director of the Neurological University Hospital Mannheim. Among numerous other awards, he was honored with the German Cancer Prize in 2019.