Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to treatment resistance heterogeneity and an immunosuppressive microenvironment, necessitating personalized therapeutics. CAR-NK cell therapy shows promise but faces challenges including target identification in heterogeneous tumors and rapid exhaustion within the TME. Cytokine-armed CAR-NK cells that self-secrete immune-activating cytokines may overcome these barriers. Circulating tumor cells (CTCs) offer dynamic insights into tumor biology, including mutation and protein profiles, enabling personalized CAR target identification. We present a pipeline integrating CTC-informed antigen selection with cytokine-armed CAR-NK therapy, leveraging minimally invasive CTC sampling and allogeneic CAR-NK potential for rapid, adaptive personalized immunotherapy. Method 6 metastatic, 7 localized). MUC4+CTCs were exclusively detected in 67% of metastatic patients, whereas 92% of all patients exhibited MSLN+CTCs, revealing the potential complementary coverage and enabling patient stratification for dual MUC4 Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1313.
Zou et al. (2026) studied this question.