Analysis of Antibody Drug Conjugate on Cellular Senescent Human Glioblastoma

Background: Glioblastoma Multiforme (GBM) is an aggressive and malignant brain tumor known for its rapid progression and unfavorable prognosis. The standard treatment options primarily involve radiation and temozolomide, however recurrence is inevitable.B7H3/CD276, an immunomodulatory transmembrane glycoprotein, demonstrates tumor-specific expression, with limited presence in normal healthy tissue, making it a promising and attractive treatment target in GBM. AbbV155 is an antibody drug conjugate that inhibits BCL-XL and specifically targets B7H3 (CD276) on GBM cells with the goal of selectively eliminating viable tumor cells.Objectives: First, we sought to confirm the presence of B7H3/CD276 in our selected cell line via ELISA testing. Once the protein was successfully identified we assessed ABBV-155’s senolytic effect on radiation induced senescent GBM cells compared to non-radiated.Methods: GBM 6 patient derived cells were cultured in vivo. Cells were allowed to grow until >50% confluency was obtained before undergoing radiation at 15 gray. Cells were maintained in culture and treatment was started 9 days post-radiation with ABBV155. A dosage response curve was calculated using a 5-step 10-fold dilution. Cells were then maintained in drug treated media for 96 hours and a Keyence Microscope was used to quantify the number of viable cells.Results: The dosage administered did not demonstrate significant efficacy between treated and non-treated cell lines.Conclusions: Future experiments will seek to utilize an expanded dose-response curve. Undoubtedly, the contrast in B7H3/CD276 expression between tumors and healthy tissue remains a compelling prospect as a biomarker and therapeutic target. Notably, antibody-drug conjugates such as ABBV155 persists as encouraging treatment modalities in this regard.