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Bioluminescent Orthotopic Model of Pancreatic Cancer Progression
Published on: June 28, 2013
Oncolytic Tanapoxvirus Variants Expressing mIL-2 and mCCL-2 Regress Human Pancreatic Cancer Xenografts in Nude Mice
Scott D Haller1, Karim Essani1
1Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI 49008-5410, USA.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death and presents the lowest 5-year survival rate of any form of cancer in the US. Only 20% of PDAC patients are suitable for surgical resection and adjuvant chemotherapy, which remains the only curative treatment. Chemotherapeutic and gene therapy treatments are associated with adverse effects and lack specificity/efficacy. In this study, we assess the oncolytic potential of immuno-oncolytic tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP-1 or mCCL2) and mouse interleukin (mIL)-2 in human pancreatic BxPc-3 cells using immunocompromised and CD-3+ T-cell-reconstituted mice. Intratumoral treatment with TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2 resulted in a regression in BxPc-3 xenograft volume compared to control in immunocompromised mice; mCCL-2 expressing TPV OV resulted in a significant difference from control at p < 0.05. Histological analysis of immunocompromised mice treated with TPV/∆66R/mCCL2 or TPV/∆66R/mIL-2 demonstrated multiple biomarkers indicative of increased severity of chronic, active inflammation compared to controls. In conclusion, TPV recombinants expressing mCCL2 and mIL-2 demonstrated a therapeutic effect via regression in BxPc-3 tumor xenografts. Considering the enhanced oncolytic potency of TPV recombinants demonstrated against PDAC in this study, further investigation as an alternative or combination treatment option for human PDAC may be warranted.
Insights
Immuno-oncolytic tanapoxvirus (TPV) recombinants engineered to express mouse monocyte chemoattractant protein-1 (mMCP-1) and mouse interleukin-2 (mIL-2) showed therapeutic potential by reducing pancreatic cancer xenograft size in mice.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Pancreatic cancer research
Background:
- Pancreatic ductal adenocarcinoma (PDAC) has a low 5-year survival rate and limited treatment options.
- Current therapies like chemotherapy and gene therapy have adverse effects and limited efficacy.
- There is a need for novel, effective treatments for PDAC.
Purpose of the Study:
- To evaluate the oncolytic potential of immuno-oncolytic tanapoxvirus (TPV) recombinants expressing mMCP-1 and mIL-2.
- To assess the efficacy of these TPV recombinants in a human pancreatic cancer xenograft model.
- To investigate the therapeutic effect of TPV recombinants in both immunocompromised and T-cell-reconstituted mice.
Main Methods:
- Human pancreatic BxPc-3 cells were used to create xenografts in mice.
- Intratumoral administration of TPV recombinants (TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2) was performed.
- Tumor volume was measured, and histological analysis was conducted on tumor tissues.
- Experiments were performed in immunocompromised mice and CD-3+ T-cell-reconstituted mice.
Main Results:
- TPV recombinants expressing mCCL2 and mIL-2 led to regression of BxPc-3 xenograft tumors compared to controls.
- TPV expressing mCCL2 showed a statistically significant difference (p < 0.05) in tumor regression.
- Histological analysis revealed biomarkers of increased chronic, active inflammation in treated tumors.
- Therapeutic effects were observed in immunocompromised mice.
Conclusions:
- TPV recombinants expressing mCCL2 and mIL-2 demonstrate oncolytic activity against PDAC xenografts.
- These TPV recombinants show therapeutic potential for pancreatic cancer treatment.
- Further investigation of TPV recombinants as an alternative or combination therapy for human PDAC is warranted.
