Abstract 2832: Identifying tumor specific surface protein markers for glioblastoma immunotherapy by single-nuclei RNA-seq

Abstract

Abstract Glioblastoma (GBM) is one of the deadliest adult brain tumors, in which the typical treatments of surgery, chemotherapy, and/or radiotherapy yield generally poor median survival. GBM is categorized into IDH-mutant subtype and IDH-wildtype subtype, which is subcategorized into proneural, classical, and mesenchymal subtypes, yet few personalized treatment options are available. The use of genetically modified chimeric antigen receptor T cells (CAR-T), such as CD19 CAR-T, has shown significant clinical efficacy in the treatment of hematological malignancies due to specific antitumor response; however, CAR-T response in GBM has been poor. Single nuclei RNA-seq (snRNA-seq) technology offers high-resolution profiling of different cell populations and their specific differential patterns. Accordingly, we developed a robust genomic analysis pipeline that can be applied to external datasets, tumor, and healthy samples. This was followed by unbiased systematic analysis of GBM tumor-specific cell surface markers using 18 single nuclei RNA sequencing (snRNA-seq) samples to identify GBM specific CAR-T targets allowing efficient tumor cells targeting and minimum off-target effects by CAR-T (1). We identified key potential targetable cell surface-specific markers and we also identified subtype-specific targets. Our findings provide insights into tumor-specific cell surface proteins that may be potential targets for engineered immunotherapy.