Abstract 564: Targeting axonal guidance with anti-ROBO1 CAR T cells: A new therapeutic strategy for malignant brain cancer
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AbstractNo standardized treatment exists for patients with recurrent glioblastoma (GBM). Given the aggressive nature of the disease and difficulty in modeling tumor recurrence, minimal efforts have been made to design rational therapies against it. The roundabout guidance receptor 1 (ROBO1) protein is involved in axonal guidance during neurodevelopment and is aberrantly upregulated in glioma where it mediates glioma cell migration. Here, we present that ROBO1 is highly expressed on the surface of malignant and treatment-refractory brain tumor initiating cells (BTICs), prompting the development of an anti-ROBO1 CAR-T cell therapy. Using the binding region of a single-domain antibody targeting ROBO1, we developed second-generation anti-ROBO1 CAR-T cells specific and effective against ROBO1-expressing BTICs. Upon antigen exposure, anti-ROBO1 CAR-T cells upregulated markers of activation and degranulation. Additionally, treatment of orthotopic and patient-derived brain tumor xenograft models with anti-ROBO1 CAR-T cells resulted in reduced tumor burden and prolonged survival, demonstrating the therapy’s therapeutic potential for treating neoplastic brain malignancies.Citation Format: Sheila Kumari Singh, Chirayu R. Chokshi, Benjamin Brakel, Martin A. Rossotti, Chitra Venugopal, Sabra Salim, Kevin Henry. Targeting axonal guidance with anti-ROBO1 CAR T cells: A new therapeutic strategy for malignant brain cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 564.
