C. Johnsen1, J. W. Ady1, K. Mojica1, A. Pugalenthi1, D. Love1, V. Longo6, P. Zanzonico6, N. G. Chen5, R. J. Aguilar5, Y. A. Yu5, A. A. Szalay5, Y. Fong2 1Memorial Sloan-Kettering Cancer Center,Surgery,New York, NY, USA 2City Of Hope National Medical Center,Surgery,Duarte, CA, USA 3University Of California – San Diego,4Department Of Radiation Medicine And Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center,San Diego, CA, USA 4University Of Würzburg,5Department Of Biochemistry, Rudolph Virchow Center For Experimental Biomedicine, And Institute For Molecular Infection Biology,Würzburg, BAVARIA, Germany 5Genelux,Research And Development,San Diego, CA, USA 6Memorial Sloan-Kettering Cancer Center,Small Animal Imaging Core,New York, NY, USA
Introduction: Cholangiocarcinoma (CC), a deadly carcinoma of the bile ducts, is clinically silent in the majority of patients until curative surgery is no longer an option. With most patients succumbing to the disease within 6 months of diagnosis, novel treatment options are needed. Oncolytic viruses are promising cancer therapy agents because they selectively infect, replicate within, and kill cancer cells. In this study, we assess the ability of the human sodium iodide symporter (hNIS) expressing recombinant oncolytic vaccinia virus GLV-1h153 to kill and image CC when combined with 131I radiotherapy.
Methods: Three human CC cell lines were assayed for infectivity, cytotoxicity and viral replication in vitro. hNIS mediated 131I radiouptake was assayed in vitro. Flank CC xenografts were treated with intratumoral GLV-1h153 alone and/or with 131I to assess tumor burden reduction. SPECT/CT was performed to visualize 131I uptake in infected tumor in vivo.
Results: All cell lines demonstrated infectivity and oncolysis in a time and concentration dependent manner. Significant viral replication was supported in all cell lines. Flank xenografts treated with GLV-1h153 combined with 131I demonstrated significant tumor reduction as compared to controls. 131I mediated SPECT/CT demonstrated significant uptake in infected tumors.
Conclusion: GLV-1h153 efficiently kills human CC in vitro. When combined with 131I, GLV-1h153 allows for SPECT/CT imaging of CC tumors and significantly reduces tumor burden in vivo. These results indicate that GLV-1h153 is a promising novel imaging and therapeutic agent for patients with CC.