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.

PubMed

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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