Mucins are a family of glycoproteins that have recently been the focus of intense investigation for fluorescence-guided surgery of cancer due to their overexpression in many malignancies. In pancreatic cancer alone there are at least twelve mucins that are upregulated or uniquely expressed. In our group, we have been developing a near infrared fluorescent labelled mAb, NIRF-AR9.6, that targets MUC16, which is overexpressed in 60-80% of pancreatic cancers. We have previously reported that in an orthotopic xenograft model of pancreatic cancer, NIRF-AR9.6 resulted in a 3.7-fold enhancement of tumor compared to surrounding pancreas, while the isotype IgG control resulted in a 2-fold increase. We also demonstrated that NIRF-AR9.6 could enhance PDAC xenografts, even with lower levels of MUC16. Moreover, initial studies showed that NIRF-AR9.6 could enhance a PDX pancreatic cancer model, consistent with MUC16 staining throughout the tumor. We are now investigating the feasibility for NIRF-AR9.6 for fluorescence-guided surgery after neoadjuvant therapy, implementing orthotopic PDX models of varying MUC16 expression, and investigating targeting multiple mucins to account for tumor heterogeneity.
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