CMET-35. PRELIMINARY SCREENING OF A NOVEL EpCAM BISPECIFIC T-CELL ENGAGER (BiTE) ANTIBODY TO TARGET A BMIC POPULATION IN HUMAN BRAIN METASTASES
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Abstract Brain Metastases (BM) are the most common type of cerebral tumor in adult, occurring at a rate 10 times greater than that of primary brain cancers. The inherent abilities of a primary tumor cell capable of initiating a BM resembles that of a cancer stem cell (CSC). Utilizing primary patient samples of BMs, we have characterized a subpopulation of CSC-like cells, termed brain metastasis-initiating cells (BMICs), which are responsible for initiating BMs. Due to the fluctuating nature of BMICs as they undergo the metastatic cycle, there currently exists a scarce few biomarkers that can faithfully identify this BMIC population. One such marker is epithelial cell adhesion molecule (EpCAM), that is utilized to identify cells of epithelial origin and has recently shown to a possible therapeutic option for the immunological treatment of BMs. Using CellectSeq, a novel methodology that combines use of phage-displayed synthetic antibody libraries and high-throughput DNA sequencing technology, a novel EpCAM-specific monoclonal antibody was generated. EpCAM-specific BiTEs were constructed to consist of two arms; one arm recognizes the tumor antigen (EpCAM) while the second is specific to CD3 antigen. The BiTEs were constructed in various conformations and dual binding specificity was confirmed using flow cytometry. Preliminary screening was performed to test the ability of BiTEs to functionally elicit EpCAM-specific cytotoxic responses in vitro. Future work will go to validate the efficacy of EpCAM-specific BiTES in targeting EpCAM positive BMICs in vivo while maintaining minimal off target cytotoxicity. Ultimately, we aim to apply the novel field of immunotherapies to block the metastatic process, transforming a uniformly fatal systemic disease into a locally controlled and eminently more treatable one.
