Oncolytic Tanapoxvirus Variants Expressing mIL-2 And mCCL-2 Regress Human Pancreatic Cancer Xenografts In Immunocompromised And Immunocompetent CAnN.Cg-Foxn1nu/Crl Nude Mice
Date of Award
Doctor of Philosophy
Karim Essani, Ph.D.
John Spitsbergen, Ph.D.
Rob Eversole, Ph.D.
Jack Hoppin, Ph.D.
Oncolytic virus, pancreatic cancer, PET/CT imaging, tanapox virus, tumor volume, virotherapy
Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in Western countries. The incidence of PDAC has increased over the last 40 years and is projected to be the second leading cause of cancer death by 2030. Despite aggressive treatment regimens, prognosis for patients diagnosed with PDAC is very poor; PDAC has the lowest 5-year survival rate for any form of cancer in the United States (US). PDAC cases are rarely detected in early stage when surgical resection can be performed and few, approximately 20%, are suitable for surgical resection which remains the only curative treatment when combined with adjuvant chemotherapy. Treatment regimens excluding surgical intervention, such as chemotherapeutic treatments, are associated with adverse effects and genetherapy strategies also struggle with lack of specificity and/or efficacy. The lack of effective treatments for this disease highlights the necessity for innovation in treatment options for patients diagnosed with early- to late-phase PDAC. Immuno-oncolytic viruses (OVs) have been of particular interest as a potential treatment option for PDAC, with differing OVs under assessment through ongoing clinical trials. In this study we assess the oncolytic potential of tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP)-1, also known as mCCL2, and mouse interleukin (mIL)-2, in human pancreatic cancer cells (Bx Pc-3), via in vitro and in vivo assays using immunocompromised and immunocompetent murine test systems. Both the wild type (wt) TPV (TPV/eGFP) and the TPV recombinants demonstrated efficient replicability and viral plaque formation in BxPc-3 cells. Intratumoral treatment with TPV/Δ66R/mCCL2 and TPV/Δ66R/mIL-2, expressing mCCL2 and mIL-2 respectively, resulted in regression of growth of BxPc-3 tumor xenografts in nude mice as compared to the control, mock injected tumors in immunocompromised subjects; mCCL-2 expressing TPV OV resulted in significant difference from control at p
Haller, Scott David, "Oncolytic Tanapoxvirus Variants Expressing mIL-2 And mCCL-2 Regress Human Pancreatic Cancer Xenografts In Immunocompromised And Immunocompetent CAnN.Cg-Foxn1nu/Crl Nude Mice" (2022). Dissertations. 3862.