Project Summary

Patients with recurrent IDH1-mutant gliomas have limited treatment options, and immunotherapies have shown only modest success in brain tumors. In the AMPLIFY-NEOVAC trial, conducted across the DKTK network, we tested a vaccine targeting the tumor-specific IDH1 mutation, alone or in combination with immune checkpoint blockade. The study demonstrated that the treatment was safe and induced strong immune responses in most patients. 

Importantly, the trial used a unique “window-of-opportunity” design, in which treatment was administered before planned tumor surgery. This enabled researchers to directly analyze treated tumor tissue and track vaccine-induced immune cells from the blood into the tumor. For the first time in patients with IDH1-mutant glioma, tumor-specific T cells induced by vaccination were shown to infiltrate and expand within brain tumors and to benefit from immune checkpoint inhibition particularly in the blood. 

Beyond evaluating a novel treatment strategy, the study established a DKTK-wide platform for reverse-translational clinical research, allowing detailed investigation of mechanisms of response and resistance in human tumors. These insights will guide the development of more effective immunotherapies for patients with IDH-mutant gliomas and beyond.