Oncolytic Newcastle disease virus expressing the co-stimulator OX40L as immunopotentiator for colorectal cancer therapy.

Abstract

NDV as an attractive candidate for oncolytic immunotherapy selectively lyses tumor cells but shows limited anti-tumor immunity. Immune co-stimulator OX40 ligand (OX40L) boosts anti-tumor immunity response by delivering a potent costimulatory signal to CD4+ and CD8+ T cells. To improve the anti-tumor immunity of NDV, the recombinant NDV expressing the murine OX40L (rNDV-mOX40L) was engineered. The viral growth kinetics was examined in CT26 cell lines. The ability of rNDV-mOX40L to express mOX40L was detected in the infected tumor cells and tumor tissues. The anti-tumor activity of rNDV-mOX40L was studied in the CT26 animal model. Tumor-specific CD4+, CD8+ and OX40+ T cells were examined by immunohistochemistry staining. The virus growth curve showed that the insertion of the mOX40L gene did not affect the growth kinetics of NDV. rNDV-mOX40L expresses mOX40L and effectively inhibits the growth of CT26 colorectal cancer in vivo. The tumor inhibition rate of the rNDV-mOX40L-treated group was increased by 15.8% compared to that of  NDV-treated group in the CT26 model. Furthermore, immunohistochemistry staining of tumor tissues removed from the CT26 model revealed that intense infiltration of tumor-specific CD4+, CD8+ T cells, especially OX40+ T cells were found in the rNDV-mOX40L-treated group. FACS showed that rNDV-mOX40L significantly enhanced the number of CD4+ and CD8+ T cells in spleen. Moreover, compared to the NDV-treated group, the level of mouse IFN-γ protein in the tumor site increased significantly in the rNDV-mOX40L-treated group. Taken together, rNDV-mOX40L exhibited superior anti-tumor immunity by stimulating tumor-specific T cells and may be a promising agent for cancer immunotherapy.

• Authors: Limin Tian, Tianyan Liu, Shan Jiang, Yukai Cao, Kai Kang, Han Su, Guiping Ren, Zhenzhong Wang, Wei Xiao, Deshan Li
• Journal: Gene therapy (Gene Ther) Vol. 30 Issue 1-2 Pg. 64-74 (02 2023) ISSN: 1476-5462 [Electronic] England
• PMID: 34602608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Adjuvants, Immunologic
• OX40 Ligand
• Interleukin-2

Topics

• Animals
• Mice
• Newcastle disease virus (genetics, metabolism)
• CD8-Positive T-Lymphocytes
• Adjuvants, Immunologic (metabolism)
• OX40 Ligand (genetics, metabolism)
• Oncolytic Viruses (genetics)
• Interleukin-2
• Colorectal Neoplasms (therapy)