Data from: Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer

Antibodies are widely available and cost-effective research tools in life
science, and antibody conjugates are now extensively used for targeted
therapy, immunohistochemical staining, or in vivo diagnostic imaging of
cancer. Significant advances in site-specific antibody labeling
technologies have enabled the production of highly characterized and
homogenous conjugates for biomedical purposes, and some recent studies
have utilized site-specific labeling to synthesize bifunctional antibody
conjugates with both imaging and drug delivery properties. While these
advances are important for the clinical safety and efficacy of such
biologics, these techniques can also be difficult, expensive, and
time-consuming. Furthermore, antibody-drug conjugates (ADCs) used for
tumor treatment generally remain distinct from conjugates used for
diagnosis. Thus, there exists a need to develop simple dual-labeling
methods for efficient therapeutic and diagnostic evaluation of antibody
conjugates in pre-clinical model systems. Here, we present a rapid and
simple method utilizing commercially available reagents for synthesizing a
dual-labeled fluorescent ADC. Further, we demonstrate the fluorescent
ADC’s utility for simultaneous targeted therapy and molecular imaging of
cancer both in vitro and in vivo. Employing non-site-specific,
amine-reactive chemistry, our novel biopharmaceutical theranostic is a
monoclonal antibody specific for a carcinoembryonic antigen (CEA)
biomarker conjugated to both paclitaxel and a near-infrared (NIR),
polyethylene glycol modified (PEGylated) fluorophore (DyLight™ 680-4xPEG).
Using in vitro systems, we demonstrate that this fluorescent ADC
selectively binds a CEA-positive pancreatic cancer cell line (BxPC-3) in
immunofluorescent staining and flow cytometry, exhibits efficient
internalization kinetics, and is cytotoxic. Model studies using a
xenograft of BxPC-3 cells in athymic mice also show the fluorescent ADC’s
efficacy in detecting tumors in vivo and inhibiting tumor growth more
effectively than equimolar amounts of unconjugated drug. Overall, our
results demonstrate that non-selective, amine-targeting chemistry is an
effective dual-labeling method for synthesizing and evaluating a
bifunctional fluorescent antibody-drug conjugate, allowing concurrent
detection, monitoring and treatment of cancer.