Abstract 1082: Development of a novel CDH17 CTC assay to monitor colorectal patient blood and cerebrospinal fluid

Abstract CDH17 is a cell adhesion molecule typically expressed in intestinal epithelial cells and pancreatic ducts. CDH17 overexpression is linked to tumor progression, metastasis and poorer prognosis and is being investigated as a target of CAR-T therapies currently in clinical development. Circulating tumor cells (CTCs) are intact cells shed from the tumor into blood or other biological fluids and can serve as a liquid biopsy for dynamic assessment of tumor protein expression. In this study we developed and validated an immunofluorescent assay to measure CDH17 expression in CTCs, and enable longitudinal monitoring of tumor CDH17 expression in patient blood and cerebrospinal fluid (CSF) samples. To optimize the CDH17 CTC assay, multiple clones were screened using positive and negative cell lines spiked into healthy donor blood. Clone E5J8Z (Cell Signaling Technologies) applied using the Leica BOND RX autostainer, provided the highest signal-to-background (S:B) ratio between positive negative cell lines. Final assay had S:B of 138 and 99.9% accuracy in distinguishing positive from negative cells.The verified assay was applied to 4 longitudinal blood and CSF samples collected from a stage IV colorectal cancer patient with brain metastasis undergoing CAR-T therapy targeting CDH17 (see table). CDH17(+) CTCs were detected in both blood and CSF, with higher CTC numbers and CDH17 expression observed in CSF samples compared to blood from the same timepoint. CTC numbers and CDH17 expression in blood and CSF decreased upon anti-CDH17 CAR-T therapy and reached undetectable levels in later samples. This study demonstrates the feasiblity and robust performance of the CDH17 CTC assay in blood and CSF of a CRC patient. Changes in CTC number and CDH17 expression can be harbingers of response to therapy and offer a minimally invasive method to longitudinally monitor biomarker expression. This approach may offer predictive and prognostic insights for patients on CDH17-targeted therapies. Citation Format: Jennifer C. Chow, Casey E. Helmicki, Rachel Ponting, Arturo B. Ramirez, Pashtoon Murtaza Kasi. Development of a novel CDH17 CTC assay to monitor colorectal patient blood and cerebrospinal fluid [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1082.