Glioblastoma multiforme (GBM) is one of the most aggressive brain tumor in pediatric patients. The current standard of care including radiation and chemotherapy is not effective in most patients due to multiple factors such as resistance and poor blood-brain barrier (BBB) penetration. The development of strategies to reduce resistance and to increase sensitivity to chemotherapy may ameliorate the problems. Glioma stem cells (GSCs) are considered the source of relapse and chemoresistance. Sensitization of temozolomide TMZ resistance in GSC is therefore integral for therapeutic efficacy. Our lab has discovered that cell surface vimentin (CSV) is presented on patient-derived GSCs. In this study, we demonstrate that the treatment of GSCs with anti-CSV antibody (86C) sensitizes them to TMZ. We found that the combination of 86C and TMZ induced additional antitumor effects in 8 out of 12 GSCs. Mechanistic study of the four resistance GSCs revealed slow re-surface rate of CSV from CSV- GSCs and low CSV expression on GSCs as possible contributing factors. GSCs with rapid CSV resurfacing from CSV- GSCs was more sensitive to combination treatment compared to GSCs with a slow recovering from CSV- GSCs. Furthermore, the metabolism study shows these four resistance cells have high intrinsic mitochondria activity compared to sensitive cells. The combination of TMZ with 86C may represent a valuable strategy to reverse GSC chemoresistance.

Citation Format: Hyangsoon Noh, Jun Yan, Konrad Gabrusiewicz, Shulin Li. Cell surface vimentin targeted mAb 86C increases sensitivity to temozolomide mediated cell death in glioma stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3869. doi:10.1158/1538-7445.AM2017-3869