PET imaging and treatment of pancreatic cancer peritoneal carcinomatosis after subcutaneous intratumoral administration of a novel oncolytic virus, CF33-hNIS-antiPDL1

Peritoneal carcinomatosis of gastrointestinal malignancies remains fatal. CF33-hNIS-antiPDL1, a chimeric orthopoxvirus expressing the human sodium iodide symporter (hNIS) and anti-human programmed death-ligand 1 antibody, has demonstrated robust preclinical activity against pancreatic adenocarcinoma (PDAC). We investigated the ability of CF33-hNIS-antiPDL1 to infect, help detect, and kill peritoneal tumors following intratumoral (i.t.) injection of subcutaneous (s.c.) tumors in vivo. Human PDAC AsPC-1-ffluc cells were inoculated in both the s.c. space and the peritoneal cavity of athymic mice. After successful tumor engraftment, s.c. tumors were injected with CF33-hNIS-antiPDL1 or PBS. We assessed the ability of CF33-hNIS-antiPDL1 to infect, replicate in, and allow the imaging of tumors at both sites (immunohistochemistry [IHC] and 124I-based positron emission tomography/computed tomography [PET/CT] imaging), tumor burden (bioluminescence imaging), and animal survival. IHC staining for hNIS confirmed expression in s.c. and peritoneal tumors following virus treatment. Compared to the controls, CF33-hNIS-antiPDL1-treated mice showed significantly decreased s.c. and peritoneal tumor burden and improved survival (p < 0.05). Notably, 2 of 8 mice showed complete regression of disease. PET/CT avidity for 124I uptake in s.c. and peritoneal tumors was visible starting at day 7 following the first i.t. dose of CF33-hNIS-antiPDL1. We show that CF33-hNIS-antiPDL1 can help detect and kill both s.c. and peritoneal tumors following s.c. i.t. treatment. [Display omitted] CF33-hNIS-anti-PD-L1 can detect both locally injected tumors and peritoneal tumors distant from the injection site in a xenograft model of PDAC. Our study demonstrates the diagnostic capability of the virus, highlighting the collective efficacy of CF33-hNIS-anti-PD-L1 with direct oncolysis and imaging/radiotherapy.