Related Experiment Video

Updated: May 23, 2025

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
12:42

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

9.4K

Expression of SIRPα-Fc by oncolytic virus enhances antitumor efficacy through tumor microenvironment reprogramming

Qingzhe Yang1, Yongheng Shu1, Yanwei Chen1

  • 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Frontiers in Immunology
|March 12, 2025
PubMed

Insights

Engineered oncolytic adenoviruses (oAdVs) expressing SIRPα-mIgG1Fc (oAd-SA) enhanced macrophage phagocytosis and T cell function. This novel immunotherapy demonstrated superior tumor regression in preclinical models, offering a promising strategy for systemic cancer treatment.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunotherapy
  • Tumor microenvironment modulation

Background:

  • Oncolytic viruses (OVs) offer targeted cancer cell killing and immune stimulation.
  • Current OV delivery, mainly intratumoral injection, limits efficacy in systemic cancers.
  • Oncolytic adenoviruses (oAdVs) are well-studied due to safety and stability.

Purpose of the Study:

  • To engineer a modified oAdV vector (pDC316-oAd-SA) expressing SIRPα-mIgG1Fc to remodel tumor-associated macrophages (TAMs).
  • To evaluate the anti-tumor efficacy of oAd-SA in vitro and in vivo.
  • To assess the impact of oAd-SA on macrophage phagocytosis and T cell immune function within the tumor microenvironment.

Main Methods:

  • Engineering of a modified oAdV vector (pDC316-oAd-SA) to express SIRPα-mIgG1Fc.
  • In vitro and in vivo evaluation of oAd-SA and a control virus (Ad-ON).
  • Assessment of macrophage phagocytosis, T cell infiltration, and immune function in murine tumor models.

Main Results:

  • oAd-SA significantly enhanced macrophage phagocytosis compared to control.
  • The modified oAdV demonstrated superior tumor regression in preclinical models.
  • oAd-SA improved T cell infiltration and specifically enhanced T cell immune function.
  • oAdVs modulated TAMs differently across tumor types, with oAd-SA promoting anti-tumor responses.

Conclusions:

  • The engineered oAd-SA vector effectively remodels TAMs, enhancing anti-tumor immunity.
  • oAd-SA shows significant potential as a therapeutic strategy for systemic cancers.
  • Targeting TAMs with oAdVs represents a promising avenue for improving cancer immunotherapy outcomes.
Keywords:
SIRPαoncolytic adenovirustumor immunotherapytumor microenvironmenttumor-associated macrophages

More Related Videos

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy08:51

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy

Published on: April 3, 2018

9.0K
Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes10:03

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes

Published on: November 11, 2016

9.7K

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
457
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
4.9K
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.5K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.0K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.5K