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

Zhifang Zhang; Annie Yang; Shyambabu Chaurasiya; Anthony K Park; Sang-In Kim; Jianming Lu; Tove Olafsen; Susanne G Warner; Yuman Fong; Yanghee Woo

doi:10.1016/j.omto.2021.12.022

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

Mol Ther Oncolytics. 2021 Dec 31:24:331-339. doi: 10.1016/j.omto.2021.12.022. eCollection 2022 Mar 17.

Authors

Zhifang Zhang¹, Annie Yang¹, Shyambabu Chaurasiya¹, Anthony K Park², Sang-In Kim¹, Jianming Lu¹, Tove Olafsen³, Susanne G Warner^{1

2}, Yuman Fong¹, Yanghee Woo^{1

2}

Affiliations

¹ Department of Surgery, City of Hope National Medical Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
² Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
³ Small Animal Imaging Core, City of Hope National Medical Center, Duarte, CA 91010, USA.

Abstract

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.

Keywords: PET/CT imaging; human sodium iodide symporter (hNIS); immune checkpoint inhibitors, ICIs); immunotherapy; preclinical; programmed death-ligand 1; virotherapy.