Oncotarget | Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma

News, Oncotarget

September 8, 2022
Research Article

“We have developed a peptide-based NIR probe, Cy5.5-N24-EGF, that shows high EGFR-specific binding specificity in canine and human UC in vitro and ex vivo.”

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BUFFALO, NY- September 8, 2022 – A new research paper was published in Oncotarget on September 6, 2022, entitled, “Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma.”

Bladder cancer (BC) is the 10th most common malignancy, affecting more than half a million people worldwide each year, and accounts for 4.6% of the total new cancer cases in the United States. With urothelial carcinoma (UC), the most common form of BC, the 5-year BC recurrence rate is nearly 78%, necessitating life-long surveillance, making it one of the costliest cancers to treat and manage. Cystoscopic visualization of bladder cancer is an essential method for initial bladder cancer detection and diagnosis, transurethral resection, and monitoring for recurrence. 

Researchers Aayush Aayush, Saloni Darji, Deepika Dhawan, Alexander Enstrom, Meaghan M. Broman, Muhammad T. Idrees, Hristos Kaimakliotis, Timothy Ratliff, Deborah Knapp, and David Thompson from Purdue University and Indiana University sought to develop a new intravesical imaging agent that is more specific and sensitive using a polypeptide based NIR (near-infrared) probe designed to detect cells bearing epidermal growth factor receptors (EGFR) that are overexpressed in 80% of urothelial carcinoma (UC) cases. The NIR imaging agent consisted of an elastin like polypeptide (ELP) fused with epidermal growth factor (EGF) and conjugated to Cy5.5 to give Cy5.5-N24-EGF as a NIR contrast agent. In addition to evaluation in human cells and tissues, the agent was tested in canine cell lines and tissue samples with naturally occurring invasive UC. 

“Dogs with naturally-occuring UC are an emerging option for a suitable large animal model of BC, where the cancer displays similar microscopic anatomy, histological appearance, biological behavior, heterogeneity, and molecular subtypes and markers to human invasive BC.”

Flow cytometry and confocal microscopy were used to test cell-associated fluorescence of the probe in T24 human UC cells, and in K9TCC-SH (high EGFR expression) and K9TCC-Original (low EGF expression) canine cell lines. The probe specifically engages these cells through EGFR within 15 min of incubation and reached saturation within a clinically relevant one-hour timeframe. 

Furthermore, ex vivo studies with resected canine and human bladder tissues showed minimal signal from normal adjacent tissue and significant NIR fluorescence labeling of tumor tissue, in good agreement with their in vitro findings. Differential expression of EGFR ex vivo was revealed by the probe and confirmed by anti-EGFR immunohistochemical staining. Taken together, their data suggests Cy5.5-ELP-EGF is a NIR probe with improved sensitivity and selectivity towards BC that shows excellent potential for clinical translation.

“While this initial proof-of-concept work focused on EGFR, future work will expand this approach by developing ELP based multi-ligand probes targeting more tumor markers. This will facilitate imaging in patients with a variety of molecular targets. By demonstrating the binding efficacy in canine tissue and cells this will set the stage for imaging canine tumors during cystoscopy in the future and enable translation to humans.”

DOI: https://doi.org/10.18632/oncotarget.28271 

Correspondence to: David Thompson – Email: davethom@purdue.edu 

Keywords: bladder cancer, elastin-like polypeptide, NIR imaging, epidermal growth factor receptor (EGFR), translational studies

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