Insights into mechanisms of T cell response and resistance in post-treatment multicellular AMPLIFY NEOVAC glioma organoids

The AMI2GO research team analyzed tumor tissue samples from brain tumor patients who were treated with an immune checkpoint inhibitor and/or a specially developed brain tumor vaccine in the Germany-wide Phase I trial AMPLIFY-NEOVAC (NCT03893903). For this purpose, a system was developed that allows tissue samples to be cultivated as a type of organ, a so-called organoid, to preserve tissue integrity. The analysis of these organoids enables prediction of treatment response in the culture dish and was carried out using modern high-throughput technologies, such as single-cell RNA sequencing. Similar sequencing enabled the identification of tumor-reactive T cell receptors (TCRs), which T cells of the immune system use to recognize and attack tumor cells. These receptors were assembled into a warehouse. The project team thus provides (1) a basis for future T cell therapies and (2) a culture system to make patient-specific therapy predictions.