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Updated: Jun 10, 2025

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
AVL-armed oncolytic vaccinia virus promotes viral replication and boosts antitumor immunity via increasing ROS levels
Jianlei Yu1, Nan An1, Jili Zhu1
1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Abstract:
Pancreatic malignant neoplasm is an extremely deadly malignancy well known for its resistance to traditional therapeutic approaches. Enhanced treatments are imperative for individuals diagnosed with pancreatic cancer (PC). Recent investigations have shed light on the wide-ranging anticancer properties of genetic therapy facilitated by oncolytic vaccinia virus. To illuminate the precise impacts of Aphrocallistes vastus lectin-armed oncolytic vaccinia virus (oncoVV-AVL) on PC, AsPC-1 and PANC-1 cells underwent treatment with oncoVV-AVL. Our findings revealed that oncoVV-AVL possesses the capacity to heighten oncolytic effects on PC cells and incite the production of diverse cytokines like tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, and interferon-I (IFN-I), without triggering antiviral responses. Additionally, oncoVV-AVL can significantly elevate the levels of ROS in PC cells, initiating an oxidative stress response that promotes viral replication, apoptosis, and autophagy. Moreover, in xenograft tumor models, oncoVV-AVL notably restrained PC growth, enhanced IFN-γ levels in the bloodstream, and reprogrammed macrophages. Our investigation indicates that oncoVV-AVL boosts the efficacy of antitumor actions against PC tumors by orchestrating reactive oxygen species-triggered viral replication, fostering M1 polarization, and reshaping the tumor microenvironment to transform cold PC tumors into hot ones. These findings imply that oncoVV-AVL could present a novel therapeutic approach for treating PC tumors.
Insights
Aphrocallistes vastus lectin-armed oncolytic vaccinia virus (oncoVV-AVL) enhances pancreatic cancer (PC) cell death and boosts antitumor immunity. This novel therapy reprograms the tumor microenvironment, offering a promising new treatment for PC.
Area of Science:
- Oncolytic virotherapy
- Cancer immunology
- Molecular oncology
Background:
- Pancreatic cancer (PC) is a deadly malignancy with limited treatment options.
- Oncolytic vaccinia virus (VV) shows promise for cancer gene therapy.
- Targeted delivery of therapeutic agents to PC is crucial.
Purpose of the Study:
- To investigate the efficacy of Aphrocallistes vastus lectin-armed oncolytic vaccinia virus (oncoVV-AVL) against pancreatic cancer.
- To elucidate the mechanisms underlying oncoVV-AVL's antitumor effects.
- To evaluate oncoVV-AVL's impact on the tumor microenvironment.
Main Methods:
- Treatment of PC cell lines (AsPC-1, PANC-1) with oncoVV-AVL.
- Analysis of cytokine production (TNF-α, IL-6, IL-8, IFN-I) and reactive oxygen species (ROS) levels.
- Assessment of viral replication, apoptosis, and autophagy induction.
- Evaluation of oncoVV-AVL in xenograft tumor models, including immune cell profiling and cytokine analysis.
Main Results:
- oncoVV-AVL demonstrated enhanced oncolytic effects on PC cells.
- oncoVV-AVL induced cytokine production without triggering antiviral responses.
- Elevated ROS levels in PC cells promoted viral replication, apoptosis, and autophagy.
- In vivo, oncoVV-AVL suppressed tumor growth, increased IFN-γ, and reprogrammed macrophages towards an M1 phenotype.
- oncoVV-AVL effectively converted "cold" PC tumors into "hot" tumors, enhancing antitumor immunity.
Conclusions:
- oncoVV-AVL exhibits significant potential as a novel therapeutic agent for pancreatic cancer.
- The mechanism involves ROS-mediated viral replication, apoptosis, autophagy, and immune modulation.
- oncoVV-AVL reshapes the tumor microenvironment, enhancing the efficacy of antitumor responses.
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